Research

Research projects

Prevention of Hereditary Breast Cancer through Personalized Optimization of Se, Zn, Fe Levels in the Body Using Dietary Supplements

Agreement No. INNOMED/I/16/NCBR/2014

Project Duration as per the Agreement: 01.10.2014-30.09.2019. The project co-financed by the European Union under the European Regional Development Fund

The project partner is the West Pomeranian University of Technology in Szczecin

Characteristics of the studied groups

The study groups, whose analyses form the basis for the results described below, were created from individuals registered in the Hereditary Cancer Center in Szczecin between 2009 and 2020. Each patient provided informed consent for the storage and use of biological material for scientific purposes. Blood and serum samples were collected between 8 AM and 2 PM, and patients fasted for at least 4 hours before collection. For the majority of patients, a sample was collected only once, but in some cases, multiple samples were taken during subsequent visits. Biological material was stored at -80°C until the element concentrations were determined. Each participant in the study completed a health and lifestyle questionnaire.

A total of 2962 healthy women were included in the prospective cohort. During 42 months of follow-up, 148 women were diagnosed with cancer.

The characteristics of the group are presented in the table.

 Cases (n=148)Healthy (n=2814)
Average age (range)56,46 (35-82)53 (33-84)

Smoking

current

former

never

40 (27,03%)

34 (22,97%)

74 (50 %)

605 (21,50%)

750 (26,65%)

1459 (51,84%)

Hormone replacement therapy / oral contraceptives

no

yes

missing data

93 (62,84%)

54 (36,49%)

1 (0,67%)

1467 (52,13%)

1316 (46,77%)

31 (1,1%)

Adnexektomia

no

yes

missing data

135 (91,22%)

9 (6,08%)

4 (2,7%)

2631 (93,50%)

175 (6,22%)

8 (0,28%)

Cancers (location)

breast

uterus

colon

melanoma

thyroid

ovary

cervix

lymphoma

bladder

lung

kidney

stomach

leukemia

myeloma

glioblastoma

pancreas

 

76 (51,4%)

12 (8,1%)

10 (6,8%)

7 (4,7%)

7 (7,73%)

6 (4,05%)

5 (3,38%)

5 (3,38%)

4 (2,7%)

4 (2,7%)

3 (2,03%)

3 (2,03%)

2 (1,35%)

2 (1,35%)

1 (0,68%)

1 (0,68%)

 

The prospective cohort included 1,324 healthy women with a mutation in the BRCA1 gene. The participants were followed up for an average of 40 months, during which 107 women were diagnosed with cancer. The characteristics of the group are presented in the table below.
Cases (n=107) Healthy (n=1217)
Average age (range) 44,25 (26-66) 40,5 (25-69)
Smoking
current
former
never
missing data

24 (22,43%)
27 (25,23%)
55 (51,4%)
1 (0,93%)

254 (20,87%)
249 (20,46%)
699 (57,44%)
15 (1,23%)
Hormone replacement therapy / oral contraceptives
no
yes
missing data

46 (43%)
60 (56,07%)
1 (0,93%)

603 (49,55%)
592 (48,64%)
22 (1,81%)
Adnexektomia
no
yes
missing data

52 (48,6%)
55 (51,4%)
0

688 (56,53%)
510 (41,92%)
19 (1,56%)
Cancers (location)
breast
ovary
cervix
peritoneum
stomach
colon
leukemia
pancreas
skin
larynx
thyroid
bladder

80 (74,8%)
15 (14%)
3  (2,8%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)












The prospective cohort included 2,956 healthy men. They were observed for an average of 76 months, during which 144 men were diagnosed with cancer. Each study participant completed a questionnaire about their health and lifestyle. Characteristics of the prospective group are presented in the table below.
  Cases (n=144) Healthy (n=2812)
Average age (range) 60,5 (36-76) 52 (31-87)
Smoking
current
former
never

42 (29,17%)
55 (38,19%)
47 (32,64 %)

829 (29,48%)
975 (34,67%)
1008 (35,85%)
Cancers (location)
prostate
skin
kidney
colon
bladder
blood
lung
liver
thyroid
pancreas
stomach
breast
esophagus
pituitary gland
salivary glands
testis

58 (40,28%)
16 (11,11%)
13 (9,03%)
13 (9,03%)
12 (8,33%)
9 (6,25%)
6 (4,17%)
4 (2,78%)
4 (2,78%)
2 (1,39%)
2 (1,39%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
















The study included 538 patients with diagnosed and histopathologically confirmed breast cancer. Blood was collected between 2009 and 2015 at the time of breast cancer diagnosis, before treatment. In 2020, information on deaths was collected during prospective observation. It was obtained from the Department of State Records - Ministry of Digitization. The mean follow-up period for living patients was 9 years (range 5-12 years). The characteristics of the group are presented in the table below.
  Alive (n=417) Deaths (n=121)
Average age (range) 55,87 (25-85) 61,07 (28-91)
Smoking
current
former
never
missing data

89 (21,3%)
112 (26,9%)
206 (49,4%)
10 (2,4%)

26 (21,5%)
27 (22,3%)
65 (53,7%)
3 (2,5%)
Estrogen receptor
positive (ER+)
negative (ER-)
missing data

287 (68,8%)
114 (27,3%)
16 (3,8%)

79 (65,3%)
32 (26,4%)
10 (8,26%)
BRCA1 mutation 50 (12%) 11 (9,1%)
Chemotherapy
yes
no
missing data

211 (50,6%)
174 (41,7%)
32 (7,7%)

65 (53,7%)
36 (29,8%)
20 (16,5%)
Radiotherapy
yes
no
missing data

244 (58,5%)
122 (29,3%)
51 (12,2%)

56 (46,3%)
35 (28,9%)
30 (24,8%)
Tamoxifen
yes
no
missing data

282 (67,6%)
122 (29,3%)
13 (3,1%)

79 (65,3%)
33 (27,3%)
9 (7,4%)
Type of operation
mastectomy
lumpectomy
missing data

261 (62,6%)
131 (31,4%)
25 (6%)

82 (67,8%)
17 (14%)
22 (18,2%)

The study included 357 patients with diagnosed and histopathologically confirmed prostate cancer. Blood was collected between 2009 and 2015 at the time of diagnosis of prostate cancer before treatment. The average follow-up period for patients was 5 years.

Gleason scale Alive (n=293)Deaths (n=102)

6

7

8

9

10

missing data

85 (29%)

164 (56%)

20 (6,8%)

17 (5,8%)

2 (0,7%)

5 (1,7%)

39 (38,2%)

35 (34,3%)

9 (8,8%)

11 (10,8%)

7 (6,9%)

2 (1,96%)
Clinical stage

1-2

3

4

missing data

7 (2,7%)

232 (79,2%)

51 (17,4%)

2 (0,7%)

4 (3,9%)

45 (44,1%)

53 (52%)

Radiotherapy

yes

no

84 (28,7%)

209 (71,3%)

24 (23,5%)

78 (76,5%)
Chemotherapy

yes

no

3 (1%)

290 (99%)

4 (3,9%)

98 (96,1%)
Hormonetherapy

yes

no

59 (20,1%)

234 (79,9%)

40 (39,2%)

62 (60,8%)
Prostatectomy

yes

no

233 (79,5%)

60 (20,5%)

33 (32,4%)

69 (67,6%)
Orchidectomy

yes

no

8 (2,7%)

285 (97,3%)

11 (10,8%)

91 (89,2%)
The group included 315 patients treated surgically between July 2009 and February 2017 due to squamous cell carcinoma of the larynx. The patients constituted over 70% of all patients operated on at the Otolaryngology Clinic of the Pomeranian Medical University in Szczecin. Clinical information was collected from all patients regarding age at onset, gender, clinical stage, radiotherapy, chemotherapy and smoking intensity (pack-years).
  n=315 %
Average age of cancer diagnosis (range) 61,1 (41-86)
Sex
women
men

49
266

15,6
84,4
Clinical stage
1
2
3
4

72
42
70
131

22,8
13,3
22,2
41,6
Pack-years (average, range) 37,11 (0-150)
Treatment
radiotherapy
chemotherapy

142
32

45,1
10,1
The study group consisted of 302 patients diagnosed with lung cancer. The patients came from the Department of Thoracic Surgery in Szczecin-Zdunowo. Patients were hospitalized between February 2010 and December 2011. Blood was collected at the time of diagnosis, before the start of treatment.
    %
Sex  
Men
Women

196
106

64,9
35,1
Average age (range) 64,2 (43-86)
Pack-years (range) 33,2 (0-232,8)
Smoking  
yes
no

283
19

93,7
6,3
Clinical stage
1
2
3
4

129
75
79
19

42,7
24,8
26,2
6,3
Radiotherapy  
yes
no

78
224

25,8
74,2
Chemotherapy  
yes
no

105
197

34,8
65,2
Histological type  
Adenocarcinoma
Squamous cell carcinoma
Large cell cancer
Large and Small Cell Mixed Carcinoma
Small Cell Carcinoma
Other

136
124
21
5
3
13

45
41,1
7
1,7
1
4,3
The study group included 100 patients with pancreatic cancer. The characteristics of the group are presented in the table below.
  New cancer diagnosis
Year of birth (range) 1930-1976
Average age at the blood donation (range) 63,4 (35-84)
Sex  
men
women

59
41
First-Degree Relatives  
with pancreatic cancer
with other cancer

4
43
Smoking  
yes
no

27
73
Pack-years (range) 28,99 (2-50)
The group included 375 patients with malignant melanoma diagnosed between 2006 and 2016. The patients' blood was secured at the time of diagnosis, before the start of treatment. The characteristics of the study group are presented in the table below.
  Alive (n=344) Deaths (n=31)
Average age (range) 54,6 (21-90) 64,3 (38-86)
Sex
women
men

218 (63%)
126 (37%)

14 (45%)
17 (55%)
Clinical stage
2
3
4-5

70 (20%)
145 (42%)
129 (38%)

1 (3,2%)
12 (39%)
18 (58%)

Research results

In the body, selenium acts through proteins into which it is incorporated in the form of selenocysteine. As a component of selenoproteins, selenium plays an enzymatic and structural role[1]. Some of the most important functions of selenoproteins include participation in the production of thyroid hormones, stimulation of the immune system, and protection against oxidative stress.[2]

Both deficiency and excess of this element may harm the body. This leads to, among others: heart disorders, heart and liver degeneration, increased risk of hypertensive disease, reduced immune system efficiency, thyroid dysfunction, impaired bone mineralization and proper tooth formation, and increased risk of cancer. [3–7]

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women over 60 years old and non-smokers have a significantly 4.5-fold reduced risk if their blood concentration is in the range of 94-104 µg/l. However, women over 60 years of age who currently smoke or have smoked in the past have a significantly 3.5-fold reduced risk of cancer if their blood selenium concentration is > 110 µg/l.

Incidence of cancer in non-smoking women over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I94-1043114Ref.Ref.Ref.
II<9411934,51,2-16,60,02*

*statistically significant result (p<0.05) P.438038

Incidence of cancer in smoking women over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I>110497Ref.Ref.Ref.
II<110251713,51,2-10,50,02*

*statistically significant result (p<0.05) P.438038

Evaluation of the cancer risk in women - BRCA1 carriers

Women under 50 years of age with blood selenium concentrations in the range of 70-80 µg/l tend to have a nearly 5-fold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women under 50 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I70-80156Ref.Ref.Ref.
II<70 & >80759044,60,6-34,10,1*

*result not statistically significant (p >0.05) P.435603

Women over 50 years of age with blood selenium concentrations in the range of 95-120 µg/l have a more than twofold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women over 50 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I95-12013156Ref.Ref.Ref.
II<95 & >120201022,31,1-4,90,03*

*statistically significant result (p <0.05) P.435603

Evaluation of the cancer risk in men

Men who do not smoke cigarettes and have selenium concentrations in the blood range of 100-110 µg/l have a nearly 4-fold reduced risk of cancer compared to men with selenium concentrations outside this range.

Cancer incidence depending on blood selenium concentration among non-smoking men (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I100-1105260Ref.Ref.Ref.
II<95202913,61,3-9,70,008*

*statistically significant result (p < 0.05) P.437898 

However, men over 60 years of age and those who have smoked cigarettes in the past or currently have a nearly 11-fold reduced risk of developing cancer if the selenium concentration in the blood is >115 µg/l, compared to men with the selenium concentration in the blood <115 µg/ l.

Cancer incidence depends on blood selenium concentration among smoking men over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<115183Ref.Ref.Ref.
II≥1155642710,91,5-79,80,0013*

*statistically significant result (p < 0.05) P.437898

The Kaplan-Meier curve for the above correlation is shown below.

-
-

Survival of patients with breast cancer

Women with breast cancer have a significantly greater chance of 10-year survival if their serum selenium concentration is >94.7 µg/l. Women with serum selenium concentration < 70 µg/l have a more than 25-fold increased risk of death compared to the subgroup with serum selenium concentration 95-102.5 µg/l.

Incidence of death depending on serum selenium concentration in women with breast cancer within 10 years of diagnosis (quarters).

QuartilesRange [µg/l]AliveDeathsHR95%CIp
I52,1-76,789462,351,12-4,550,01*
II76,8-85,1105291,520,76-3,020,23
III85,2-94,6105291,951,01-3,760,047*
IV94,7-171,511817Ref.Ref.Ref.

*statistically significant result (p<0.05)

The incidence of death depends on serum selenium concentration in women with breast cancer within 10 years of diagnosis (ranges).

QuartilesRange [µg/l]AliveDeathsOR95%CIp
I< 703228Ref.Ref.Ref.
II95-102,562227,16,7-121,2<0,0001*

*statistically significant result (p<0.05)

The above results are part of the publication by Szwiec M et al., Serum Selenium Level Predicts 10-Years Survival after Breast Cancer; Nutrients 2021, 13(3), 953. [8]

Survival of patients with prostate cancer

Men with prostate cancer and serum selenium concentration in the range of 85-105 µg/l have a significantly reduced risk of death by over 8 times compared to the subgroup with serum selenium concentration below 70 µg/l.

The incidence of death depends on serum selenium concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤7061338,63,4-21,7<0,0001*
II85-105956Ref.Ref.Ref.

*statistically significant result (p<0.05)

Survival of patients with lung cancer

It has been observed that people whose serum selenium concentration is >67.4 µg/l have a greater chance of longer survival after a lung cancer diagnosis than people with a low serum selenium concentration (<55.1 µg/l).

Frequency of deaths depending on serum selenium concentration in patients with stage I lung cancer within 3 years of diagnosis (tertiles).

TertilesRange [µg/l]totalOR95%CIp
I33,46-57,91432,731,21-6,110,01*
II57,92-68,86421,880,83-4,280,13
III69,29-108,2744Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are part of the publication by Pietrzak S et al., Influence of the selenium level on overall survival in lung cancer, Journal of Trace Elements in Medicine and Biology 2019, 56:46-51.[9]

Survival of patients with pancreatic cancer

Patients diagnosed with pancreatic cancer have a 3-fold greater chance of 6-month survival if their serum selenium concentration is ≥ 63.67 µg/l compared to patients with selenium concentration below this value.

The incidence of death depends on serum selenium concentration in patients with pancreatic cancer within 6 months of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsOR95%CIp
I>< 63,6724330,40,1-0,970,03*
II≥ 63,672211Ref.Ref.Ref.

The above results are part of the publication by Lener M et al., Serum concentration of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer, Cancer Res Treat., 2016, 48(3):1056-1064.[10]

Survival of patients with melanoma

Patients diagnosed with malignant melanoma have a significantly greater chance of 10-year survival if their serum selenium concentration is higher than 96 µg/l. Patients with serum selenium concentration 96 µg/l.

The incidence of death depends on serum selenium concentration in patients with malignant melanoma within 10 years of diagnosis (quarters).

QuartilesRange [µg/l]AliveDeathsHR95%CIp
I56,7-76,278165,831,32-25,80,02*
II76,4-85,018673,370,7-16,30,13
III85,15-96,068863,340,67-16,70,14
IV96,15-168922Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are the subject of the publication by Rogoża-Janiszewska E. et al., Serum selenium level and the 10-year survival after melanoma, Biomedicines, 2021.[11]

Arsenic and its compounds are among the most recognized toxins. According to the classification of the International Agency for Research on Cancer (IARC), arsenic and its compounds have been categorized as Group 1[12] carcinogens, meaning they are definite human carcinogens. The clinical manifestations resulting from inhalation or ingestion of arsenic compounds vary widely. Depending on the concentration, duration of exposure, and route of absorption, the effects of arsenic interaction with tissues range from relatively benign, such as hypopigmentation, to life-threatening tumors (WHO). Based on existing literature, it can be concluded that not only high but also slightly elevated arsenic concentrations may be linked to cancers, especially in women.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with an arsenic concentration in blood below 0.6 µg/l have a significant, almost 5-fold reduced risk of developing cancers, especially breast cancer, compared to women with an arsenic concentration above 0.6 µg/l (OR=4.7; p=0 .0004; 95%CI:1.9-11.7).

Incidence of breast cancer depending on arsenic concentration in blood (selected ranges)

GroupRangeNew cancer diagnosisUnaffectedOR95%CIp
I<0,65735Ref.Ref.Ref.
II0,6-0,81187233,71,4-100,01*
III0,82-1,25217194,31,6-11-50,002*
IV>1,25327096,62,6-17,1<0,0001*
Selected ranges
I<0,65735Ref.Ref.Ref.
II≥0,67122224,71,9-11,70,0004*

*statistically significant result (p<0.05) P.425602

The Kaplan-Meier curve for the above correlation is shown below.

-

The above results are the subject of the publication Marciniak W. et al., Blood arsenic levels and the risk of familial breast cancer in Poland, Int J Cancer, 2020, 146 (10): 2721-2727.[13]

Evaluation of the cancer risk in women - BRCA1 carriers

Women with an arsenic concentration in blood below 0.85 µg/l have a significantly reduced risk of developing cancer by approximately two times compared to women with an arsenic concentration above 0.85 µg/l (OR=2.55; p=0.0006; 95% CI:1.47-4.43).

The incidence of cancer depends on the concentration of arsenic in the blood.

GroupRangeNew cancer diagnosisUnaffectedOR95%CIp
I<0,8518513Ref.Ref.Ref.
II>0,85495482,551,47-4,430,0006*

*statistically significant result (p<0.05)

The above results are part of the publication by Marciniak W. et al.,  Blood Arsenic Levels as a Marker of Breast Cancer Risk among BRCA1 Carriers, Cancers 2021, 13(13), 3345. [14]

Evaluation of the cancer risk in men

Men whose blood arsenic concentration is between 0.7 and 1.14 µg/l have a nearly 5-fold reduced risk of cancer.

Cancer incidence in men depending on arsenic concentration in blood (selected ranges)

GroupRange [µg/l].New cancer diagnosisUnaffectedOR95%CIp
I0,7-1,1428788Ref.Ref.Ref.
II<0,7 & > 1,1411620034,81,1-2,50,03*

*statistically significant result (p<0.05) P.437896

Survival of patients with prostate cancer

Men with serum arsenic concentration in the range of 0.7-1.0 µg/l have a significantly reduced risk of death by more than 3 times compared to the subgroup with serum arsenic concentration < 0.7 µg/l.

The incidence of death depends on serum arsenic concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

GroupRange [µg/l]DeathsAliveOR95%CIp
I<0,722503,181,63-6,220,0009*
II0,7-1,022159Ref.Ref.Ref.
III>1,021831,830,95-3,520,085

*statistically significant result (p<0.05)

According to the classification of the International Agency for Research on Cancer (IARC), cadmium and its compounds have been categorized as Group 1 [12] human carcinogens. The adverse effects of cadmium and its compounds can lead to kidney diseases, cardiovascular diseases, hypertension, anemia, liver damage, disorders of the reproductive organs, immune system disorders, deficiencies of iron, copper, and zinc, as well as the development of cancer. Numerous studies describe increased levels of cadmium in the biological material of individuals who have developed malignant tumors of the prostate, kidney, bladder, pancreas, and breast.

The literature mentions three main sources of cadmium: diet, smoking, and occupational exposure[25]. The concentration of cadmium in food products is strongly dependent on the content of this element in the environment - air, soil, and water[25]. The concentration of cadmium in the blood is strongly correlated with smoking tobacco products. In non-smokers, Cd concentration is lower compared to smokers[26]. The occupational group most exposed to cadmium are workers in the zinc, steel, and copper industries, as well as in the production of nickel-cadmium batteries, solar cells, and jewelry[27].

Evaluation of the cancer risk in women - BRCA1 non-carriers

The table below shows the distribution of subjects in our chosen range. The risk of cancer is reduced more than 8 times among women whose concentration is in the range of 0.28-0.33 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking women over 50 years of age (selected range)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,28-0,331126Ref.Ref.Ref.
II<0,28 & >0,33446658,341,1-61,10,009*

*statistically significant result (p<0.05) P.437608

Evaluation of the cancer risk in women - BRCA1 carriers

In women under 51 years of age with blood cadmium concentration ≤0.32 µg/l, the risk is reduced by more than 8 times compared to women with higher cadmium levels.

Cancer incidence depending on blood cadmium concentration in women under 51 years of age (selected range)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤0,32192Ref.Ref.Ref.
II>0,32222448,301,1-62,460,013*

*statistically significant result (p <0.05) PAT.237085

The above results are the subject of a publication sent for publication by Derkacz R. et al., Blood Cadmium Level and the Risk of Cancer in Women with BRCA1 Mutations, Cancers, 2021.[28]

Evaluation of the cancer risk in men

Men who have never smoked cigarettes and whose blood cadmium concentration is below 0.14 µg/l have a nearly 6-fold reduced risk of cancer compared to men with a blood cadmium concentration above 0.28 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking men (quarters)

QuartilesRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,03-0,144260Ref.Ref.Ref.
II0,14-0,2172571,770,51-6,120,54
III0,21-0,28152493,921,28-11,960,02
IV0,28-2,34212425,641,91-16,670,0004*

*statistically significant result (p<0.05) P.437897

Zinc is an essential element for the proper functioning of the body. It plays a protective role against free radicals, including being part of superoxide dismutase (SOD2). It is also involved in immune processes, contributes to the proper functioning of the skin and mucous membranes, and is involved in storing and secreting insulin from the pancreas. Zinc maintains the ion balance of other trace elements, including selenium, magnesium, and copper, and also plays a detoxifying role with heavy metals. Deficiency of this element leads to serious disorders such as immunodeficiencies, inflammation (including SARS-CoV-2), impaired wound healing, reduced fertility, and vision problems [29,30].

It has been observed that zinc levels change in cancer cells[31]. Normal prostate epithelial cells accumulate zinc, while in cancer cells the level of this element is significantly reduced.[32] Zinc is believed to have anti-cancer effects by inhibiting the growth of cancer cells and activating apoptosis. There are known studies assessing the relationship between zinc concentration and the risk of cancer, but their results are divergent. Some of these studies say that serum zinc concentration is higher in people with cancer [33-35], while others say that the level is lower.[36] The results of research conducted so far also suggest that an appropriate amount of zinc in the diet has a chemopreventive effect. People whose diet is rich in zinc have a lower risk of lung cancer than people following a zinc-poor diet (OR 0.71; 95% CI 0.5-0.99). [37] The risk of colorectal cancer is also lower with a zinc-rich diet (RR 0.86; 95% CI 0.73-1.02).[38] However, zinc supplementation in very high doses above 100 mg/day (the recommended daily intake of zinc is 8 mg/day for women and 12 mg/day for men) has the opposite effect, significantly increasing the risk of prostate cancer (RR 2.29; 95% CI 1.06 – 4.95, p=0.03).[39] The results of research conducted in our Center are presented below.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women over 50 years of age with a zinc concentration in the blood in the range of 5600-6100 µg/l have a 6.5-fold reduced risk of cancer compared to women with a zinc concentration below 5600 µg/l, and a 3.5-fold reduced risk compared to women with zinc concentration above 6100 µg/l.

Incidence of cancer depending on the concentration of zinc in the blood in non-smoking women over 50 years of age.

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<5600201986,51-89-22,120,0008*
II5600-61003192Ref.Ref.Ref.
III>6100223993,51,04-11,940,029

*statistically significant result (p<0.05) P.437571

Evaluation of the cancer risk in women - BRCA1 carriers

Women with a mutation in the BRCA1 gene who do not smoke cigarettes have an almost 3-fold reduced risk of cancer if their zinc level is in the range of 6000-6700 µg/l. Such a correlation cannot be found among cigarette smokers.

Incidence of cancers depending on the concentration of zinc in the blood in women carriers of mutations in the BRCA1 gene who did not smoke cigarettes (selected ranges)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I6000-67008218Ref.Ref.Ref.
II<6000&>6700494812,81,3-6,00,006*

*statistically significant result (p<0.05) P.425603

Evaluation of the cancer risk in men

Men who have not smoked cigarettes have a nearly four-fold reduced risk of cancer if their blood zinc concentration is in the range of 5600-6350 µg/l.

Częstość występowania raków w zależności od stężenia cynku we krwi u mężczyzn niepalących (wybrane zakresy)

QuartilesRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I5600-63505318Ref.Ref.Ref.
II<5600&>6350416873,81,5-9,70,0018*

*statistically significant result (p<0.05) P.437894

Survival of patients with breast cancer

Women diagnosed with breast cancer and serum zinc concentration > 1000 µg/l have a nearly 6-fold reduced risk of death compared to women with zinc concentration < 700 µg/l.

The table shows the incidence of death according to serum zinc concentration in women with breast cancer (n=538).

Incidence of death depending on serum zinc concentration in women with breast cancer within 10 years of diagnosis (selected ranges)

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤70033255,682,09-15,420,0003*
II700-850181542,240,91-5,530,088
III851-1000158361,710,68-4,310,30
IV≥1000456Ref.Ref.Ref.

*statistically significant result (p<0.05) P.434767

Survival of patients with prostate cancer

Men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200 µg/l have an almost 4-fold reduced risk of death compared to men whose serum zinc concentration is < 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (quarters)

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤760,3856348,43,31-21,33<0,0001*
II760,39-839,6375142,580,94-7,060,095
III839,64-931,7278111,950,69-5,530,31
IV≥931,73836Ref.Ref.Ref.

*statistically significant result (p<0.05)

Among men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200, a nearly 4-fold reduced risk of death was observed compared to men whose zinc concentration is lower than 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (selected ranges)

GroupRange [µg/l]AliveDeathsOR95%CIp
I<900180543,71,09-12,480,03*
II1000-1200373Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are the subject of patent application P.437046.

Survival of patients with laryngeal cancer

Among people with laryngeal cancer, the risk of death was more than twice reduced in patients with zinc concentrations above 688 µg/l in serum compared to those with concentrations <580 µg/l.

Frequency of deaths depending on serum zinc concentration in patients with laryngeal cancer within 5 years of diagnosis (tertiles)

GroupRange [µg/l]AliveDeathsOR95%CIp
I357,76-580,3852522,451,4-4,4<0,01*
II584,46-688,8967371,350,8-2,40,31
III688,94-1317,877631Ref.Ref.Ref.

*statistically significant result (p<0.05) P.427370

The above results are the subject of the publication Lubiński J. et al., Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes, Biomolecules2021, 11, 865.[40]

Copper performs various functions in the structure of proteins and as a catalyst thanks to the ability to change the degree of oxidation and reduction and occurs in the oxidized (Cu2+) or reduced (Cu+) state. Copper ions can participate in a wide range of interactions with proteins, enabling the formation of complex structures and mediating complex biochemical reactions.[41,42] Copper, like other trace elements, is, on the one hand, essential for the body, but on the other hand, it is very dangerous. . In general, however, conditions that are characterized by general or cell-specific copper accumulation are rare and most often occur as a result of specific genetic disorders.[43]

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women under 50 with blood copper concentrations between 850-1000 µg/l have an almost three-fold reduced risk of cancer.

Incidence of cancer in non-smoking women under 50 years of age with no mutations in the BRCA1 gene (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I850-100016493Ref.Ref.Ref.
II<850131562,61,2-5,50,02*

*statistically significant result (p<0.05) P.438572

Environmental lead contamination is an ongoing problem for developing societies. The toxic effect of lead mainly concerns its effect on the hematopoietic system[44], the peripheral and central nervous system[45] and the gastrointestinal tract[46]. Due to the ubiquity of lead, virtually every person is exposed to contact with this element. Lead toxicity leads, among other things, to changes in the activity of many enzymes and disturbances in the functions of free and structural proteins in the cell[47]. Many studies suggest that an important molecular mechanism of lead toxicity is its participation in the formation of free oxygen radicals, which play a large role in the formation of intracellular damage and in the pathogenesis of many diseases, including malignant tumors[48]. According to the IARC classification of carcinogens, lead and its compounds belong to groups 2a and 2b, i.e. potentially carcinogenic [12].

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by almost 9 times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤81372Ref.Ref.Ref.
II>82610948,841,2-65,410,006*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in women - BRCA1 carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by three times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤88217Ref.Ref.Ref.
II>8878122,91,4-6,10,002*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in men

Men under 60 years of age and non-smokers have an almost 8-fold reduced risk of developing the disease if their lead concentration is lower than 13.5 µg/l.

Cancer incidence depends on lead concentration in non-smoking men under 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<13,51217Ref.Ref.Ref.
II>13,5164477,81,02-59,00,017*

*statistically significant result (p<0.05) P.437899

Men over 60 years of age, non-smokers have a four-fold reduced risk of cancer if their lead concentration is in the range of 20-50 µg/l in whole blood.

Cancer incidence depends on lead concentration in non-smoking men over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I20-50374Ref.Ref.Ref.
II<20 & >5015904,11,1-14,80,02*

*statistically significant result (p<0.05) P.437899

Manganese (Mn) is an essential nutrient involved in properly functioning the immune system, regulation of blood sugar levels and cellular energy, reproduction, digestion, bone growth, blood clotting and homeostasis, and defense against reactive oxygen species. The functions performed by manganese metalloproteins include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [49] Mn acts as a cofactor for various enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase, and Mn superoxide dismutase (Mn-SOD) [50]. Mn tends to accumulate in the liver, pancreas, bones, and brain [50].

The literature contains studies describing the correlation between serum Mn concentration and the risk of breast and colorectal cancer. However, the published studies are retrospective, which makes them unreliable for the conclusion that manganese is a marker of cancer risk. In our Center, we assessed the correlation between manganese concentration and survival of women with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer, whose serum manganese concentration is in the range of 1-10 µg/l, have a significantly reduced risk of death by over 1.5 times compared to other women.

The incidence of death depends on serum manganese concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I1,0-10,019749Ref.Ref.Ref.
II<1 & > 10204871,551,09-2,200,01*

*statistically significant result (p<0.05) P.438040

Chromium (Cr) is an element widely distributed in the Earth's crust. This element in small amounts is necessary for the proper functioning of the body, playing a role in the metabolic processes of glucose, some proteins, and fats [51–53]. Increased doses of chromium may have a strong toxic effect, destructively affecting the liver, kidneys, and hematopoietic system, and causing cancer [51,54,55]. Cr(VI) has been found to have a strong mutagenic effect. The results of association studies indicate a relationship between the concentration of chromium in the blood and the risk of cancer in the head, neck, and oral cavity.

In our Center, work was carried out on the correlation between serum chromium concentration and survival of women diagnosed with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer whose serum chromium concentration is in the range of 0.20-3.5 µg/l have a significantly reduced risk of death by almost two times.

Incidence of death depending on serum chromium concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I0,20-3,520254Ref.Ref.Ref.
II<0,20 & > 3,5199821,81,28-2,540,0002*

*statistically significant result (p<0.05) P.438042

Women who smoke cigarettes and have been diagnosed with breast cancer have a significantly reduced risk of death by almost 4.5 times if their serum chromium concentration is higher than 0.5 µg/l.

Incidence of death depending on serum chromium concentration in smokers with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I<0,5157564,461,39-14,260,01*
II≥0,5383Ref.Ref.Ref.

*statistically significant result (p<0.05) P.438042

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Research

Research projects

Prevention of Hereditary Breast Cancer through Personalized Optimization of Se, Zn, Fe Levels in the Body Using Dietary Supplements

Agreement No. INNOMED/I/16/NCBR/2014

Project Duration as per the Agreement: 01.10.2014-30.09.2019. The project co-financed by the European Union under the European Regional Development Fund

The project partner is the West Pomeranian University of Technology in Szczecin

Characteristics of the studied groups

The study groups, whose analyses form the basis for the results described below, were created from individuals registered in the Hereditary Cancer Center in Szczecin between 2009 and 2020. Each patient provided informed consent for the storage and use of biological material for scientific purposes. Blood and serum samples were collected between 8 AM and 2 PM, and patients fasted for at least 4 hours before collection. For the majority of patients, a sample was collected only once, but in some cases, multiple samples were taken during subsequent visits. Biological material was stored at -80°C until the element concentrations were determined. Each participant in the study completed a health and lifestyle questionnaire.

A total of 2962 healthy women were included in the prospective cohort. During 42 months of follow-up, 148 women were diagnosed with cancer.

The characteristics of the group are presented in the table.

 Cases (n=148)Healthy (n=2814)
Average age (range)56,46 (35-82)53 (33-84)

Smoking

current

former

never

40 (27,03%)

34 (22,97%)

74 (50 %)

605 (21,50%)

750 (26,65%)

1459 (51,84%)

Hormone replacement therapy / oral contraceptives

no

yes

missing data

93 (62,84%)

54 (36,49%)

1 (0,67%)

1467 (52,13%)

1316 (46,77%)

31 (1,1%)

Adnexektomia

no

yes

missing data

135 (91,22%)

9 (6,08%)

4 (2,7%)

2631 (93,50%)

175 (6,22%)

8 (0,28%)

Cancers (location)

breast

uterus

colon

melanoma

thyroid

ovary

cervix

lymphoma

bladder

lung

kidney

stomach

leukemia

myeloma

glioblastoma

pancreas

 

 

76 (51,4%)

12 (8,1%)

10 (6,8%)

7 (4,7%)

7 (7,73%)

6 (4,05%)

5 (3,38%)

5 (3,38%)

4 (2,7%)

4 (2,7%)

3 (2,03%)

3 (2,03%)

2 (1,35%)

2 (1,35%)

1 (0,68%)

1 (0,68%)

The prospective cohort included 1,324 healthy women with a mutation in the BRCA1 gene. The participants were followed up for an average of 40 months, during which 107 women were diagnosed with cancer. The characteristics of the group are presented in the table below.
Cases (n=107) Healthy (n=1217)
Average age (range) 44,25 (26-66) 40,5 (25-69)
Smoking
current
former
never
missing data

24 (22,43%)
27 (25,23%)
55 (51,4%)
1 (0,93%)

254 (20,87%)
249 (20,46%)
699 (57,44%)
15 (1,23%)
Hormone replacement therapy / oral contraceptives
no
yes
missing data

46 (43%)
60 (56,07%)
1 (0,93%)

603 (49,55%)
592 (48,64%)
22 (1,81%)
Adnexektomia
no
yes
missing data

52 (48,6%)
55 (51,4%)
0

688 (56,53%)
510 (41,92%)
19 (1,56%)
Cancers (location)
breast
ovary
cervix
peritoneum
stomach
colon
leukemia
pancreas
skin
larynx
thyroid
bladder

80 (74,8%)
15 (14%)
3  (2,8%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)
1 (0,9%)












The prospective cohort included 2,956 healthy men. They were observed for an average of 76 months, during which 144 men were diagnosed with cancer. Each study participant completed a questionnaire about their health and lifestyle. Characteristics of the prospective group are presented in the table below.
  Cases (n=144) Healthy (n=2812)
Average age (range) 60,5 (36-76) 52 (31-87)
Smoking
current
former
never

42 (29,17%)
55 (38,19%)
47 (32,64 %)

829 (29,48%)
975 (34,67%)
1008 (35,85%)
Cancers (location)
prostate
skin
kidney
colon
bladder
blood
lung
liver
thyroid
pancreas
stomach
breast
esophagus
pituitary gland
salivary glands
testis

58 (40,28%)
16 (11,11%)
13 (9,03%)
13 (9,03%)
12 (8,33%)
9 (6,25%)
6 (4,17%)
4 (2,78%)
4 (2,78%)
2 (1,39%)
2 (1,39%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
1 (0,69%)
















The study included 538 patients with diagnosed and histopathologically confirmed breast cancer. Blood was collected between 2009 and 2015 at the time of breast cancer diagnosis, before treatment. In 2020, information on deaths was collected during prospective observation. It was obtained from the Department of State Records - Ministry of Digitization. The mean follow-up period for living patients was 9 years (range 5-12 years). The characteristics of the group are presented in the table below.
  Alive (n=417) Deaths (n=121)
Average age (range) 55,87 (25-85) 61,07 (28-91)
Smoking
current
former
never
missing data

89 (21,3%)
112 (26,9%)
206 (49,4%)
10 (2,4%)

26 (21,5%)
27 (22,3%)
65 (53,7%)
3 (2,5%)
Estrogen receptor
positive (ER+)
negative (ER-)
missing data

287 (68,8%)
114 (27,3%)
16 (3,8%)

79 (65,3%)
32 (26,4%)
10 (8,26%)
BRCA1 mutation 50 (12%) 11 (9,1%)
Chemotherapy
yes
no
missing data

211 (50,6%)
174 (41,7%)
32 (7,7%)

65 (53,7%)
36 (29,8%)
20 (16,5%)
Radiotherapy
yes
no
missing data

244 (58,5%)
122 (29,3%)
51 (12,2%)

56 (46,3%)
35 (28,9%)
30 (24,8%)
Tamoxifen
yes
no
missing data

282 (67,6%)
122 (29,3%)
13 (3,1%)

79 (65,3%)
33 (27,3%)
9 (7,4%)
Type of operation
mastectomy
lumpectomy
missing data

261 (62,6%)
131 (31,4%)
25 (6%)

82 (67,8%)
17 (14%)
22 (18,2%)

The study included 357 patients with diagnosed and histopathologically confirmed prostate cancer. Blood was collected between 2009 and 2015 at the time of diagnosis of prostate cancer before treatment. The average follow-up period for patients was 5 years.

Gleason scale Alive (n=293)Deaths (n=102)

6

7

8

9

10

missing data

85 (29%)

164 (56%)

20 (6,8%)

17 (5,8%)

2 (0,7%)

5 (1,7%)

39 (38,2%)

35 (34,3%)

9 (8,8%)

11 (10,8%)

7 (6,9%)

2 (1,96%)
Clinical stage

1-2

3

4

missing data

7 (2,7%)

232 (79,2%)

51 (17,4%)

2 (0,7%)

4 (3,9%)

45 (44,1%)

53 (52%)

Radiotherapy

yes

no

84 (28,7%)

209 (71,3%)

24 (23,5%)

78 (76,5%)
Chemotherapy

yes

no

3 (1%)

290 (99%)

4 (3,9%)

98 (96,1%)
Hormonetherapy

yes

no

59 (20,1%)

234 (79,9%)

40 (39,2%)

62 (60,8%)
Prostatectomy

yes

no

233 (79,5%)

60 (20,5%)

33 (32,4%)

69 (67,6%)
Orchidectomy

yes

no

8 (2,7%)

285 (97,3%)

11 (10,8%)

91 (89,2%)
The group included 315 patients treated surgically between July 2009 and February 2017 due to squamous cell carcinoma of the larynx. The patients constituted over 70% of all patients operated on at the Otolaryngology Clinic of the Pomeranian Medical University in Szczecin. Clinical information was collected from all patients regarding age at onset, gender, clinical stage, radiotherapy, chemotherapy and smoking intensity (pack-years).
  n=315 %
Average age of cancer diagnosis (range) 61,1 (41-86)
Sex
women
men

49
266

15,6
84,4
Clinical stage
1
2
3
4

72
42
70
131

22,8
13,3
22,2
41,6
Pack-years (average, range) 37,11 (0-150)
Treatment
radiotherapy
chemotherapy

142
32

45,1
10,1
The study group consisted of 302 patients diagnosed with lung cancer. The patients came from the Department of Thoracic Surgery in Szczecin-Zdunowo. Patients were hospitalized between February 2010 and December 2011. Blood was collected at the time of diagnosis, before the start of treatment.
    %
Sex  
Men
Women

196
106

64,9
35,1
Average age (range) 64,2 (43-86)
Pack-years (range) 33,2 (0-232,8)
Smoking  
yes
no

283
19

93,7
6,3
Clinical stage
1
2
3
4

129
75
79
19

42,7
24,8
26,2
6,3
Radiotherapy  
yes
no

78
224

25,8
74,2
Chemotherapy  
yes
no

105
197

34,8
65,2
Histological type  
Adenocarcinoma
Squamous cell carcinoma
Large cell cancer
Large and Small Cell Mixed Carcinoma
Small Cell Carcinoma
Other

136
124
21
5
3
13

45
41,1
7
1,7
1
4,3
The study group included 100 patients with pancreatic cancer. The characteristics of the group are presented in the table below.
  New cancer diagnosis
Year of birth (range) 1930-1976
Average age at the blood donation (range) 63,4 (35-84)
Sex  
men
women

59
41
First-Degree Relatives  
with pancreatic cancer
with other cancer

4
43
Smoking  
yes
no

27
73
Pack-years (range) 28,99 (2-50)
The group included 375 patients with malignant melanoma diagnosed between 2006 and 2016. The patients' blood was secured at the time of diagnosis, before the start of treatment. The characteristics of the study group are presented in the table below.
  Alive (n=344) Deaths (n=31)
Average age (range) 54,6 (21-90) 64,3 (38-86)
Sex
women
men

218 (63%)
126 (37%)

14 (45%)
17 (55%)
Clinical stage
2
3
4-5

70 (20%)
145 (42%)
129 (38%)

1 (3,2%)
12 (39%)
18 (58%)

Research results

In the body, selenium acts through proteins into which it is incorporated in the form of selenocysteine. As a component of selenoproteins, selenium plays an enzymatic and structural role[1]. Some of the most important functions of selenoproteins include participation in the production of thyroid hormones, stimulation of the immune system, and protection against oxidative stress.[2]

Both deficiency and excess of this element may harm the body. This leads to, among others: heart disorders, heart and liver degeneration, increased risk of hypertensive disease, reduced immune system efficiency, thyroid dysfunction, impaired bone mineralization and proper tooth formation, and increased risk of cancer. [3–7]

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women over 60 years old and non-smokers have a significantly 4.5-fold reduced risk if their blood concentration is in the range of 94-104 µg/l. However, women over 60 years of age who currently smoke or have smoked in the past have a significantly 3.5-fold reduced risk of cancer if their blood selenium concentration is > 110 µg/l.

Incidence of cancer in non-smoking women over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I94-1043114Ref.Ref.Ref.
II<9411934,51,2-16,60,02*

*statistically significant result (p<0.05) P.438038

Incidence of cancer in smoking women over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I>110497Ref.Ref.Ref.
II<110251713,51,2-10,50,02*

*statistically significant result (p<0.05) P.438038

Evaluation of the cancer risk in women - BRCA1 carriers

Women under 50 years of age with blood selenium concentrations in the range of 70-80 µg/l tend to have a nearly 5-fold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women under 50 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I70-80156Ref.Ref.Ref.
II<70 & >80759044,60,6-34,10,1*

*result not statistically significant (p >0.05) P.435603

Women over 50 years of age with blood selenium concentrations in the range of 95-120 µg/l have a more than twofold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women over 50 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I95-12013156Ref.Ref.Ref.
II<95 & >120201022,31,1-4,90,03*

*statistically significant result (p <0.05) P.435603

Evaluation of the cancer risk in men

Men who do not smoke cigarettes and have selenium concentrations in the blood range of 100-110 µg/l have a nearly 4-fold reduced risk of cancer compared to men with selenium concentrations outside this range.

Cancer incidence depending on blood selenium concentration among non-smoking men (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I100-1105260Ref.Ref.Ref.
II<95202913,61,3-9,70,008*

*statistically significant result (p 115 µg/l , compared to men with blood selenium concentration <115 µg/l.

Cancer incidence depends on blood selenium concentration among smoking men over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<115183Ref.Ref.Ref.
II≥1155642710,91,5-79,80,0013*

*statistically significant result (p < 0.05) P.437898

The Kaplan-Meier curve for the above correlation is shown below.

-
-

Survival of patients with breast cancer

Women with breast cancer have a significantly greater chance of 10-year survival if their serum selenium concentration is >94.7 µg/l. Women with serum selenium concentration < 70 µg/l have a more than 25-fold increased risk of death compared to the subgroup with serum selenium concentration 95-102.5 µg/l.

Incidence of death depending on serum selenium concentration in women with breast cancer within 10 years of diagnosis (quarters).

QuartilesRange [µg/l]AliveDeathsHR95%CIp
I52,1-76,789462,351,12-4,550,01*
II76,8-85,1105291,520,76-3,020,23
III85,2-94,6105291,951,01-3,760,047*
IV94,7-171,511817Ref.Ref.Ref.

*statistically significant result (p<0.05)

The incidence of death depends on serum selenium concentration in women with breast cancer within 10 years of diagnosis (ranges).

QuartilesRange [µg/l]AliveDeathsOR95%CIp
I< 703228Ref.Ref.Ref.
II95-102,562227,16,7-121,2<0,0001*

*statistically significant result (p<0.05)

The above results are part of the publication by Szwiec M et al., Serum Selenium Level Predicts 10-Years Survival after Breast Cancer; Nutrients 2021, 13(3), 953. [8]

Survival of patients with prostate cancer

Men with prostate cancer and serum selenium concentration in the range of 85-105 µg/l have a significantly reduced risk of death by over 8 times compared to the subgroup with serum selenium concentration below 70 µg/l.

The incidence of death depends on serum selenium concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤7061338,63,4-21,7<0,0001*
II85-105956Ref.Ref.Ref.

*statistically significant result (p<0.05)

Survival of patients with lung cancer

It has been observed that people whose serum selenium concentration is >67.4 µg/l have a greater chance of longer survival after a lung cancer diagnosis than people with a low serum selenium concentration (<55.1 µg/l).

Frequency of deaths depending on serum selenium concentration in patients with stage I lung cancer within 3 years of diagnosis (tertiles).

TertilesRange [µg/l]totalOR95%CIp
I33,46-57,91432,731,21-6,110,01*
II57,92-68,86421,880,83-4,280,13
III69,29-108,2744Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are part of the publication by Pietrzak S et al., Influence of the selenium level on overall survival in lung cancer, Journal of Trace Elements in Medicine and Biology 2019, 56:46-51.[9]

Survival of patients with pancreatic cancer

Patients diagnosed with pancreatic cancer have a 3-fold greater chance of 6-month survival if their serum selenium concentration is ≥ 63.67 µg/l compared to patients with selenium concentration below this value.

The incidence of death depends on serum selenium concentration in patients with pancreatic cancer within 6 months of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsOR95%CIp
I>< 63,6724330,40,1-0,970,03*
II≥ 63,672211Ref.Ref.Ref.

The above results are part of the publication by Lener M et al., Serum concentration of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer, Cancer Res Treat., 2016, 48(3):1056-1064.[10]

Survival of patients with melanoma

Patients diagnosed with malignant melanoma have a significantly greater chance of 10-year survival if their serum selenium concentration is higher than 96 µg/l. Patients with serum selenium concentration 96 µg/l.

The incidence of death depends on serum selenium concentration in patients with malignant melanoma within 10 years of diagnosis (quarters).

QuartilesRange [µg/l]AliveDeathsHR95%CIp
I56,7-76,278165,831,32-25,80,02*
II76,4-85,018673,370,7-16,30,13
III85,15-96,068863,340,67-16,70,14
IV96,15-168922Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are the subject of the publication by Rogoża-Janiszewska E. et al., Serum selenium level and the 10-year survival after melanoma, Biomedicines, 2021.[11]

Arsenic and its compounds are among the most recognized toxins. According to the classification of the International Agency for Research on Cancer (IARC), arsenic and its compounds have been categorized as Group 1[12] carcinogens, meaning they are definite human carcinogens. The clinical manifestations resulting from inhalation or ingestion of arsenic compounds vary widely. Depending on the concentration, duration of exposure, and route of absorption, the effects of arsenic interaction with tissues range from relatively benign, such as hypopigmentation, to life-threatening tumors (WHO). Based on existing literature, it can be concluded that not only high but also slightly elevated arsenic concentrations may be linked to cancers, especially in women.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with an arsenic concentration in blood below 0.6 µg/l have a significant, almost 5-fold reduced risk of developing cancers, especially breast cancer, compared to women with an arsenic concentration above 0.6 µg/l (OR=4.7; p=0 .0004; 95%CI:1.9-11.7).

Incidence of breast cancer depending on arsenic concentration in blood (selected ranges)

GroupRangeNew cancer diagnosisUnaffectedOR95%CIp
I<0,65735Ref.Ref.Ref.
II0,6-0,81187233,71,4-100,01*
III0,82-1,25217194,31,6-11-50,002*
IV>1,25327096,62,6-17,1<0,0001*
Selected ranges
I<0,65735Ref.Ref.Ref.
II≥0,67122224,71,9-11,70,0004*

*statistically significant result (p<0.05) P.425602

The Kaplan-Meier curve for the above correlation is shown below.

-

The above results are the subject of the publication Marciniak W. et al., Blood arsenic levels and the risk of familial breast cancer in Poland, Int J Cancer, 2020, 146 (10): 2721-2727.[13]

Evaluation of the cancer risk in women - BRCA1 carriers

Women with an arsenic concentration in blood below 0.85 µg/l have a significantly reduced risk of developing cancer by approximately two times compared to women with an arsenic concentration above 0.85 µg/l (OR=2.55; p=0.0006; 95% CI:1.47-4.43).

The incidence of cancer depends on the concentration of arsenic in the blood.

GroupRangeNew cancer diagnosisUnaffectedOR95%CIp
I<0,8518513Ref.Ref.Ref.
II>0,85495482,551,47-4,430,0006*

*statistically significant result (p<0.05)

The above results are part of the publication by Marciniak W. et al.,  Blood Arsenic Levels as a Marker of Breast Cancer Risk among BRCA1 Carriers, Cancers 2021, 13(13), 3345. [14]

Evaluation of the cancer risk in men

Men whose blood arsenic concentration is between 0.7 and 1.14 µg/l have a nearly 5-fold reduced risk of cancer.

Cancer incidence in men depending on arsenic concentration in blood (selected ranges)

GroupRange [µg/l].New cancer diagnosisUnaffectedOR95%CIp
I0,7-1,1428788Ref.Ref.Ref.
II<0,7 & > 1,1411620034,81,1-2,50,03*

*statistically significant result (p<0.05) P.437896

Survival of patients with prostate cancer

Men with serum arsenic concentration in the range of 0.7-1.0 µg/l have a significantly reduced risk of death by more than 3 times compared to the subgroup with serum arsenic concentration < 0.7 µg/l.

The incidence of death depends on serum arsenic concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

GroupRange [µg/l]DeathsAliveOR95%CIp
I<0,722503,181,63-6,220,0009*
II0,7-1,022159Ref.Ref.Ref.
III>1,021831,830,95-3,520,085

*statistically significant result (p<0.05)

According to the classification of the International Agency for Research on Cancer (IARC), cadmium and its compounds have been categorized as Group 1 [12] human carcinogens. The adverse effects of cadmium and its compounds can lead to kidney diseases, cardiovascular diseases, hypertension, anemia, liver damage, disorders of the reproductive organs, immune system disorders, deficiencies of iron, copper, and zinc, as well as the development of cancer. Numerous studies describe increased levels of cadmium in the biological material of individuals who have developed malignant tumors of the prostate, kidney, bladder, pancreas, and breast.

The literature mentions three main sources of cadmium: diet, smoking, and occupational exposure[25]. The concentration of cadmium in food products is strongly dependent on the content of this element in the environment - air, soil, and water[25]. The concentration of cadmium in the blood is strongly correlated with smoking tobacco products. In non-smokers, Cd concentration is lower compared to smokers[26]. The occupational group most exposed to cadmium are workers in the zinc, steel, and copper industries, as well as in the production of nickel-cadmium batteries, solar cells, and jewelry[27].

Evaluation of the cancer risk in women - BRCA1 non-carriers

The table below shows the distribution of subjects in our chosen range. The risk of cancer is reduced more than 8 times among women whose concentration is in the range of 0.28-0.33 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking women over 50 years of age (selected range)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,28-0,331126Ref.Ref.Ref.
II<0,28 & >0,33446658,341,1-61,10,009*

*statistically significant result (p<0.05) P.437608

Evaluation of the cancer risk in women - BRCA1 carriers

In women under 51 years of age with blood cadmium concentration ≤0.32 µg/l, the risk is reduced by more than 8 times compared to women with higher cadmium levels.

Cancer incidence depending on blood cadmium concentration in women under 51 years of age (selected range)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤0,32192Ref.Ref.Ref.
II>0,32222448,301,1-62,460,013*

*statistically significant result (p <0.05) PAT.237085

The above results are the subject of a publication sent for publication by Derkacz R. et al., Blood Cadmium Level and the Risk of Cancer in Women with BRCA1 Mutations, Cancers, 2021.[28]

Evaluation of the cancer risk in men

Men who have never smoked cigarettes and whose blood cadmium concentration is below 0.14 µg/l have a nearly 6-fold reduced risk of cancer compared to men with a blood cadmium concentration above 0.28 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking men (quarters)

QuartilesRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,03-0,144260Ref.Ref.Ref.
II0,14-0,2172571,770,51-6,120,54
III0,21-0,28152493,921,28-11,960,02
IV0,28-2,34212425,641,91-16,670,0004*

*statistically significant result (p<0.05) P.437897

Zinc is an essential element for the proper functioning of the body. It plays a protective role against free radicals, including being part of superoxide dismutase (SOD2). It is also involved in immune processes, contributes to the proper functioning of the skin and mucous membranes, and is involved in storing and secreting insulin from the pancreas. Zinc maintains the ion balance of other trace elements, including selenium, magnesium, and copper, and also plays a detoxifying role with heavy metals. Deficiency of this element leads to serious disorders such as immunodeficiencies, inflammation (including SARS-CoV-2), impaired wound healing, reduced fertility, and vision problems [29,30].

It has been observed that zinc levels change in cancer cells[31]. Normal prostate epithelial cells accumulate zinc, while in cancer cells the level of this element is significantly reduced.[32] Zinc is believed to have anti-cancer effects by inhibiting the growth of cancer cells and activating apoptosis. There are known studies assessing the relationship between zinc concentration and the risk of cancer, but their results are divergent. Some of these studies say that serum zinc concentration is higher in people with cancer [33-35], while others say that the level is lower.[36] The results of research conducted so far also suggest that an appropriate amount of zinc in the diet has a chemopreventive effect. People whose diet is rich in zinc have a lower risk of lung cancer than people following a zinc-poor diet (OR 0.71; 95% CI 0.5-0.99). [37] The risk of colorectal cancer is also lower with a zinc-rich diet (RR 0.86; 95% CI 0.73-1.02).[38] However, zinc supplementation in very high doses above 100 mg/day (the recommended daily intake of zinc is 8 mg/day for women and 12 mg/day for men) has the opposite effect, significantly increasing the risk of prostate cancer (RR 2.29; 95% CI 1.06 – 4.95, p=0.03).[39] The results of research conducted in our Center are presented below.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women over 50 years of age with a zinc concentration in the blood in the range of 5600-6100 µg/l have a 6.5-fold reduced risk of cancer compared to women with a zinc concentration below 5600 µg/l, and a 3.5-fold reduced risk compared to women with zinc concentration above 6100 µg/l.

Incidence of cancer depending on the concentration of zinc in the blood in non-smoking women over 50 years of age.

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<5600201986,51-89-22,120,0008*
II5600-61003192Ref.Ref.Ref.
III>6100223993,51,04-11,940,029

*statistically significant result (p<0.05) P.437571

Evaluation of the cancer risk in women - BRCA1 carriers

Women with a mutation in the BRCA1 gene who do not smoke cigarettes have an almost 3-fold reduced risk of cancer if their zinc level is in the range of 6000-6700 µg/l. Such a correlation cannot be found among cigarette smokers.

Incidence of cancers depending on the concentration of zinc in the blood in women carriers of mutations in the BRCA1 gene who did not smoke cigarettes (selected ranges)

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I6000-67008218Ref.Ref.Ref.
II<6000&>6700494812,81,3-6,00,006*

*statistically significant result (p<0.05) P.425603

Evaluation of the cancer risk in men

Men who have not smoked cigarettes have a nearly four-fold reduced risk of cancer if their blood zinc concentration is in the range of 5600-6350 µg/l.

Częstość występowania raków w zależności od stężenia cynku we krwi u mężczyzn niepalących (wybrane zakresy)

QuartilesRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I5600-63505318Ref.Ref.Ref.
II<5600&>6350416873,81,5-9,70,0018*

*statistically significant result (p<0.05) P.437894

Survival of patients with breast cancer

Women diagnosed with breast cancer and serum zinc concentration > 1000 µg/l have a nearly 6-fold reduced risk of death compared to women with zinc concentration < 700 µg/l.

The table shows the incidence of death according to serum zinc concentration in women with breast cancer (n=538).

Incidence of death depending on serum zinc concentration in women with breast cancer within 10 years of diagnosis (selected ranges)

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤70033255,682,09-15,420,0003*
II700-850181542,240,91-5,530,088
III851-1000158361,710,68-4,310,30
IV≥1000456Ref.Ref.Ref.

*statistically significant result (p<0.05) P.434767

Survival of patients with prostate cancer

Men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200 µg/l have an almost 4-fold reduced risk of death compared to men whose serum zinc concentration is < 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (quarters)

GroupRange [µg/l]AliveDeathsOR95%CIp
I≤760,3856348,43,31-21,33<0,0001*
II760,39-839,6375142,580,94-7,060,095
III839,64-931,7278111,950,69-5,530,31
IV≥931,73836Ref.Ref.Ref.

*statistically significant result (p<0.05)

Among men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200, a nearly 4-fold reduced risk of death was observed compared to men whose zinc concentration is lower than 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (selected ranges)

GroupRange [µg/l]AliveDeathsOR95%CIp
I<900180543,71,09-12,480,03*
II1000-1200373Ref.Ref.Ref.

*statistically significant result (p<0.05)

The above results are the subject of patent application P.437046.

Survival of patients with laryngeal cancer

Among people with laryngeal cancer, the risk of death was more than twice reduced in patients with zinc concentrations above 688 µg/l in serum compared to those with concentrations <580 µg/l.

Frequency of deaths depending on serum zinc concentration in patients with laryngeal cancer within 5 years of diagnosis (tertiles)

GroupRange [µg/l]AliveDeathsOR95%CIp
I357,76-580,3852522,451,4-4,4<0,01*
II584,46-688,8967371,350,8-2,40,31
III688,94-1317,877631Ref.Ref.Ref.

*statistically significant result (p<0.05) P.427370

The above results are the subject of the publication Lubiński J. et al., Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes, Biomolecules2021, 11, 865.[40]

Copper performs various functions in the structure of proteins and as a catalyst thanks to the ability to change the degree of oxidation and reduction and occurs in the oxidized (Cu2+) or reduced (Cu+) state. Copper ions can participate in a wide range of interactions with proteins, enabling the formation of complex structures and mediating complex biochemical reactions.[41,42] Copper, like other trace elements, is, on the one hand, essential for the body, but on the other hand, it is very dangerous. . In general, however, conditions that are characterized by general or cell-specific copper accumulation are rare and most often occur as a result of specific genetic disorders.[43]

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women under 50 with blood copper concentrations between 850-1000 µg/l have an almost three-fold reduced risk of cancer.

Incidence of cancer in non-smoking women under 50 years of age with no mutations in the BRCA1 gene (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I850-100016493Ref.Ref.Ref.
II<850131562,61,2-5,50,02*

*statistically significant result (p<0.05) P.438572

Environmental lead contamination is an ongoing problem for developing societies. The toxic effect of lead mainly concerns its effect on the hematopoietic system[44], the peripheral and central nervous system[45] and the gastrointestinal tract[46]. Due to the ubiquity of lead, virtually every person is exposed to contact with this element. Lead toxicity leads, among other things, to changes in the activity of many enzymes and disturbances in the functions of free and structural proteins in the cell[47]. Many studies suggest that an important molecular mechanism of lead toxicity is its participation in the formation of free oxygen radicals, which play a large role in the formation of intracellular damage and in the pathogenesis of many diseases, including malignant tumors[48]. According to the IARC classification of carcinogens, lead and its compounds belong to groups 2a and 2b, i.e. potentially carcinogenic [12].

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by almost 9 times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤81372Ref.Ref.Ref.
II>82610948,841,2-65,410,006*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in women - BRCA1 carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by three times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤88217Ref.Ref.Ref.
II>8878122,91,4-6,10,002*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in men

Men under 60 years of age and non-smokers have an almost 8-fold reduced risk of developing the disease if their lead concentration is lower than 13.5 µg/l.

Cancer incidence depends on lead concentration in non-smoking men under 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<13,51217Ref.Ref.Ref.
II>13,5164477,81,02-59,00,017*

*statistically significant result (p<0.05) P.437899

Men over 60 years of age, non-smokers have a four-fold reduced risk of cancer if their lead concentration is in the range of 20-50 µg/l in whole blood.

Cancer incidence depends on lead concentration in non-smoking men over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I20-50374Ref.Ref.Ref.
II<20 & >5015904,11,1-14,80,02*

*statistically significant result (p<0.05) P.437899

Manganese (Mn) is an essential nutrient involved in properly functioning the immune system, regulation of blood sugar levels and cellular energy, reproduction, digestion, bone growth, blood clotting and homeostasis, and defense against reactive oxygen species. The functions performed by manganese metalloproteins include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [49] Mn acts as a cofactor for various enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase, and Mn superoxide dismutase (Mn-SOD) [50]. Mn tends to accumulate in the liver, pancreas, bones, and brain [50].

The literature contains studies describing the correlation between serum Mn concentration and the risk of breast and colorectal cancer. However, the published studies are retrospective, which makes them unreliable for the conclusion that manganese is a marker of cancer risk. In our Center, we assessed the correlation between manganese concentration and survival of women with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer, whose serum manganese concentration is in the range of 1-10 µg/l, have a significantly reduced risk of death by over 1.5 times compared to other women.

The incidence of death depends on serum manganese concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I1,0-10,019749Ref.Ref.Ref.
II<1 & > 10204871,551,09-2,200,01*

*statistically significant result (p<0.05) P.438040

Chromium (Cr) is an element widely distributed in the Earth's crust. This element in small amounts is necessary for the proper functioning of the body, playing a role in the metabolic processes of glucose, some proteins, and fats [51–53]. Increased doses of chromium may have a strong toxic effect, destructively affecting the liver, kidneys, and hematopoietic system, and causing cancer [51,54,55]. Cr(VI) has been found to have a strong mutagenic effect. The results of association studies indicate a relationship between the concentration of chromium in the blood and the risk of cancer in the head, neck, and oral cavity.

In our Center, work was carried out on the correlation between serum chromium concentration and survival of women diagnosed with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer whose serum chromium concentration is in the range of 0.20-3.5 µg/l have a significantly reduced risk of death by almost two times.

Incidence of death depending on serum chromium concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I0,20-3,520254Ref.Ref.Ref.
II<0,20 & > 3,5199821,81,28-2,540,0002*

*statistically significant result (p<0.05) P.438042

Women who smoke cigarettes and have been diagnosed with breast cancer have a significantly reduced risk of death by almost 4.5 times if their serum chromium concentration is higher than 0.5 µg/l.

Incidence of death depending on serum chromium concentration in smokers with breast cancer within 10 years of diagnosis (selected ranges).

GroupRange [µg/l]AliveDeathsHR95%CIp
I<0,5157564,461,39-14,260,01*
II≥0,5383Ref.Ref.Ref.

*statistically significant result (p<0.05) P.438042

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Research

Research projects

Prevention of Hereditary Breast Cancer through Personalized Optimization of Se, Zn, Fe Levels in the Body Using Dietary Supplements

Agreement No. INNOMED/I/16/NCBR/2014

Project Duration as per the Agreement: 01.10.2014-30.09.2019. The project co-financed by the European Union under the European Regional Development Fund

The project partner is the West Pomeranian University of Technology in Szczecin

Characteristics of the studied groups

The study groups, whose analyses form the basis for the results described below, were created from individuals registered in the Hereditary Cancer Center in Szczecin between 2009 and 2020. Each patient provided informed consent for the storage and use of biological material for scientific purposes. Blood and serum samples were collected between 8 AM and 2 PM, and patients fasted for at least 4 hours before collection. For the majority of patients, a sample was collected only once, but in some cases, multiple samples were taken during subsequent visits. Biological material was stored at -80°C until the element concentrations were determined. Each participant in the study completed a health and lifestyle questionnaire.

A total of 2962 healthy women were included in the prospective cohort. During 42 months of follow-up, 148 women were diagnosed with cancer.

The characteristics of the group are presented in the table.

 

 

Cases (n=148)

Healthy (n=2814)

Average age (range)

56,46 (35-82)

53 (33-84)

Smoking

current

former

never

 

40 (27,03%)

34 (22,97%)

74 (50 %)

 

605 (21,50%)

750 (26,65%)

1459 (51,84%)

Hormone replacement therapy / oral contraceptives

no

yes

missing data

 

93 (62,84%)

54 (36,49%)

1 (0,67%)

 

1467 (52,13%)

1316 (46,77%)

31 (1,1%)

Adnexektomia

no

yes

missing data

 

135 (91,22%)

9 (6,08%)

4 (2,7%)

 

2631 (93,50%)

175 (6,22%)

8 (0,28%)

Cancers (location)

breast

uterus

colon

melanoma

thyroid

ovary

cervix

lymphoma

bladder

lung

kidney

stomach

leukemia

myeloma

glioblastoma

pancreas

 

76 (51,4%)

12 (8,1%)

10 (6,8%)

7 (4,7%)

7 (7,73%)

6 (4,05%)

5 (3,38%)

5 (3,38%)

4 (2,7%)

4 (2,7%)

3 (2,03%)

3 (2,03%)

2 (1,35%)

2 (1,35%)

1 (0,68%)

1 (0,68%)

 

Do kohorty prospektywnej włączono 1324 zdrowe (bez zdiagnozowanego nowotworu złośliwego) kobiety, u których wykryto mutację w genie BRCA1. Uczestniczki zostały poddane średnio 40 miesięcznej obserwacji, w trakcie której u 107 kobiet zdiagnozowano nowotwór złośliwy.

The characteristics of the group are presented in the table.

 


 

Cases (n=107)

Healthy (n=1217)

Average age (range)

44,25 (26-66)

40,5 (25-69)

Smoking

current

former

never

missing data

 

24 (22,43%)

27 (25,23%)

55 (51,4%)

1 (0,93%)

 

254 (20,87%)

249 (20,46%)

699 (57,44%)

15 (1,23%)

Hormone replacement therapy / oral contraceptives

no

yes

missing data

 

46 (43%)

60 (56,07%)

1 (0,93%)

 

603 (49,55%)

592 (48,64%)

22 (1,81%)

Adnexektomia

no

yes

missing data

 

52 (48,6%)

55 (51,4%)

0

 

688 (56,53%)

510 (41,92%)

19 (1,56%)

Cancers (location)

breast

ovary

cervix

peritoneum

stomach

colon

leukemia

pancreas

skin

larynx

thyroid

bladder

 

80 (74,8%)

15 (14%)

3  (2,8%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

1 (0,9%)

 

 

Do kohorty prospektywnej włączono zdrowych (bez zdiagnozowanego nowotworu złośliwego) 2956 mężczyzn. Zostali oni poddani średnio 76 miesięcznej obserwacji, w trakcie której u 144 mężczyzn zdiagnozowano nowotwór złośliwy. Każdy z uczestników badania wypełnił ankietę o stanie zdrowia oraz stylu życia.

Charakterystykę grupy prospektywnej przedstawiono w poniższej tabeli.

 

 

Cases (n=144)

Healthy (n=2812)

Average age (range)

60,5 (36-76)

52 (31-87)

Smoking

current

former

never

 

42 (29,17%)

55 (38,19%)

47 (32,64 %)

 

829 (29,48%)

975 (34,67%)

1008 (35,85%)

Cancers (location)

prostate

skin

kidney

colon

bladder

blood

lung

liver

thyroid

pancreas

stomach

breast

esophagus

pituitary gland

salivary glands

testis

 

58 (40,28%)

16 (11,11%)

13 (9,03%)

13 (9,03%)

12 (8,33%)

9 (6,25%)

6 (4,17%)

4 (2,78%)

4 (2,78%)

2 (1,39%)

2 (1,39%)

1 (0,69%)

1 (0,69%)

1 (0,69%)

1 (0,69%)

1 (0,69%)

 

Do badań włączono 538 pacjentek ze zdiagnozowanym i potwierdzonym histopatologicznie rakiem piersi. Krew została zebrana w latach 2009-2015 w momencie diagnozy raka piersi, przed rozpoczęciem leczenia. W 2020 roku zebrano informację o zgonach w trakcie obserwacji prospektywnej. Uzyskano ją z Departamentu Ewidencji Państwowych – Ministerstwa Cyfryzacji. Średni okres obserwacji dla pacjentek żyjących wyniósł 9 lat (zakres 5-12 lat).

Charakterystyka grupy została przedstawiona w poniższej tabeli.

 

 

Alive (n=417)

Deaths (n=121)

Average age (range)

55,87 (25-85)

61,07 (28-91)

Smoking

current

former

never

missing data

 

89 (21,3%)

112 (26,9%)

206 (49,4%)

10 (2,4%)

 

26 (21,5%)

27 (22,3%)

65 (53,7%)

3 (2,5%)

Estrogen receptor

positive (ER+)

negative (ER-)

missing data

 

287 (68,8%)

114 (27,3%)

16 (3,8%)

 

79 (65,3%)

32 (26,4%)

10 (8,26%)

BRCA1 mutation

50 (12%)

11 (9,1%)

Chemotherapy

yes

no

missing data

 

211 (50,6%)

174 (41,7%)

32 (7,7%)

 

65 (53,7%)

36 (29,8%)

20 (16,5%)

Radiotherapy

yes

no

missing data

 

244 (58,5%)

122 (29,3%)

51 (12,2%)

 

56 (46,3%)

35 (28,9%)

30 (24,8%)

Tamoxifen

yes

no

missing data

 

282 (67,6%)

122 (29,3%)

13 (3,1%)

 

79 (65,3%)

33 (27,3%)

9 (7,4%)

Type of operation

mastectomy

lumpectomy

missing data

 

261 (62,6%)

131 (31,4%)

25 (6%)

 

82 (67,8%)

17 (14%)

22     18,2%)

The study included 357 patients with diagnosed and histopathologically confirmed prostate cancer. Blood was collected between 2009 and 2015 at the time of diagnosis of prostate cancer before treatment. The average follow-up period for patients was 5 years.

 

 

Alive (n=293)

Deaths (n=102)

Gleason scale

6

7

8

9

10

missing data

 

85 (29%)

164 (56%)

20 (6,8%)

17 (5,8%)

2 (0,7%)

5 (1,7%)

 

39 (38,2%)

35 (34,3%)

9 (8,8%)

11 (10,8%)

7 (6,9%)

2 (1,96%)

Clinical stage

1-2

3

4

missing data

 

7 (2,7%)

232 (79,2%)

51 (17,4%)

2 (0,7%)

 

4 (3,9%)

45 (44,1%)

53 (52%)

Radiotherapy

yes

no

 

84 (28,7%)

209 (71,3%)

 

24 (23,5%)

78 (76,5%)

Chemotherapy

yes

no

 

3 (1%)

290 (99%)

 

4 (3,9%)

98 (96,1%)

Hormonetherapy

yes

no

 

59 (20,1%)

234 (79,9%)

 

40 (39,2%)

62 (60,8%)

Prostatectomy

yes

no

 

233 (79,5%)

60 (20,5%)

 

33 (32,4%)

69 (67,6%)

Orchidectomy

yes

no

 

8 (2,7%)

285 (97,3%)

 

11 (10,8%)

91     89,2%)

The group included 315 patients treated surgically between July 2009 and February 2017 due to squamous cell carcinoma of the larynx. The patients constituted over 70% of all patients operated on at the Otolaryngology Clinic of the Pomeranian Medical University in Szczecin. Clinical information was collected from all patients regarding age at onset, gender, clinical stage, radiotherapy, chemotherapy and smoking intensity (pack-years).

 

n=315

%

Average age of cancer diagnosis (range)

61,1 (41-86)

 

Sex

women

men

 

49

266

 

15,6

84,4

Clinical stage

1

2

3

4

 

72

42

70

131

 

22,8

13,3

22,2

41,6

Pack-years (average, range)

37,11 (0-150)

 

Treatment

radiotherapy

chemotherapy

 

142

32

 

45,1

10,1

The study group consisted of 302 patients diagnosed with lung cancer. The patients came from the Department of Thoracic Surgery in Szczecin-Zdunowo. Patients were hospitalized between February 2010 and December 2011. Blood was collected at the time of diagnosis, before the start of treatment.

 

 

 

%

Sex

 

Men

Women

 

 

196

106

 

 

64,9

35,1

Average age (range)

64,2 (43-86)

Pack-years (range)

33,2 (0-232,8)

Smoking

 

yes

no

 

 

283

19

 

 

93,7

6,3

Clinical stage

1

2

3

4

 

129

75

79

19

 

42,7

24,8

26,2

6,3

Radiotherapy

 

yes

no

 

 

78

224

 

 

25,8

74,2

Chemotherapy

 

yes

no

 

 

105

197

 

 

34,8

65,2

Histological type

 

Adenocarcinoma

Squamous cell carcinoma

Large cell cancer

Large and Small Cell Mixed Carcinoma

Small Cell Carcinoma

Other

 

 

136

124

21

5

3

13

 

 

45

41,1

7

1,7

1

4,3

Do grupy badanej włączono 100 pacjentów z rakiem trzustki.

Charakterystyka grupy została przedstawiona w poniższej tabeli.

 

 

New cancer diagnosis

Year of birth (range)

1930-1976

Average age at the blood donation (range)

63,4 (35-84)

Sex

 

men

women

 

 

59

41

First-Degree Relatives

 

with pancreatic cancer

with other cancer

 

 

4

43

Smoking

 

yes

no

 

 

27

73

Pack-years (range)

28,99 (2-50)

Do grupy włączono 375 pacjentów ze zdiagnozowanym czerniakiem złośliwym zdiagnozowanych w latach 2006-2016. Krew pacjentów została zabezpieczona w momencie diagnozy, przed rozpoczęciem leczenia.

Charakterystyka grupy badanej została przedstawiona w poniższej tabeli.

 

 

Alive (n=344)

Deaths (n=31)

Average age (range)

54,6 (21-90)

64,3 (38-86)

Sex

women

men

 

218 (63%)

126 (37%)

 

14 (45%)

17 (55%)

Clinical stage

2

3

4-5

 

70 (20%)

145 (42%)

129 (38%)

 

1 (3,2%)

12 (39%)

18 (58%)

 

Research results

W organizmie selen działa poprzez białka, do których jest wbudowany w postaci selenocysteiny. Jako składnik selenobiałek selen odgrywa rolę enzymatyczną, jak i strukturalną[1]. Do jednych z ważniejszych funkcji selenobiałek należy udział w produkcji hormonów tarczycy, pobudzanie układu immunologicznego, oraz ochrona przed stresem oksydacyjnym.[2] Zarówno niedobór jak i nadmiar tego pierwiastka może mieć niekorzystny wpływ na organizm. Prowadzi to do m.in. do zaburzeń pracy serca, zwyrodnienia serca i wątroby, zwiększenia ryzyka choroby nadciśnieniowej, ograniczenia sprawności układu odpornościowego, zaburzenia funkcji tarczycy, zaburzenia mineralizacji kości i prawidłowego wykształcenia zębów oraz zwiększenia ryzyka chorób nowotworowych. [3–7]

 

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women over 60 years old and non-smokers have a significantly 4.5-fold reduced risk if their blood concentration is in the range of 94-104 µg/l. However, women over 60 years of age who currently smoke or have smoked in the past have a significantly 3.5-fold reduced risk of cancer if their blood selenium concentration is > 110 µg/l.

Incidence of cancer in non-smoking women over 60 years of age (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

94-104

3

114

Ref.

Ref.

Ref.

II

<94

11

93

4,5

1,2-16,6

0,02*

*statistically significant result (p<0.05) P.438038

Incidence of cancer in smoking women over 60 years of age (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

>110

4

97

Ref.

Ref.

Ref.

II

<110

25

171

3,5

1,2-10,5

0,02*

*wynik istotny statystycznie (p<0,05)  P.438038

Evaluation of the cancer risk in women - BRCA1 carriers

Women under 50 years of age with blood selenium concentrations in the range of 70-80 µg/l tend to have a nearly 5-fold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women under 50 years of age (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

70-80

1

56

Ref.

Ref.

Ref.

II

<70 & >80

75

904

4,6

0,6-34,1

0,1*

*wynik nieistotny statystycznie (p>0,05) P.435603

Women over 50 years of age with blood selenium concentrations in the range of 95-120 µg/l have a more than twofold reduced risk of cancer compared to women with selenium concentrations outside the presented range.

Cancer incidence depending on blood selenium concentration among women over 50 years of age (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

95-120

13

156

Ref.

Ref.

Ref.

II

<95 & >120

20

102

2,3

1,1-4,9

0,03*

*statistically significant result (p <0.05) P.435603

Evaluation of the cancer risk in men

Men who do not smoke cigarettes and have selenium concentrations in the blood range of 100-110 µg/l have a nearly 4-fold reduced risk of cancer compared to men with selenium concentrations outside this range.

Cancer incidence depending on blood selenium concentration among non-smoking men (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

100-110

5

260

Ref.

Ref.

Ref.

II

<95

20

291

3,6

1,3-9,7

0,008*

*wynik istotny statystycznie (p <0,05)  P.437898

However, men over 60 years of age and those who have smoked cigarettes in the past or currently have a nearly 11-fold reduced risk of developing cancer if the selenium concentration in the blood is >115 µg/l, compared to men with the selenium concentration in the blood <115 µg/ l.

Cancer incidence depends on blood selenium concentration among smoking men over 60 years of age (selected ranges).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

<115

1

83

Ref.

Ref.

Ref.

II

≥115

56

427

10,9

1,5-79,8

0,0013*

*statistically significant result (p < 0.05) P.437898

The Kaplan-Meier curve for the above correlation is shown below.

-
-

Survival of patients with breast cancer

Women with breast cancer have a significantly greater chance of 10-year survival if their serum selenium concentration is >94.7 µg/l. Women with serum selenium concentration < 70 µg/l have a more than 25-fold increased risk of death compared to the subgroup with serum selenium concentration 95-102.5 µg/l.

Incidence of death depending on serum selenium concentration in women with breast cancer within 10 years of diagnosis (quarters).

Quartiles

Range [µg/l]

Alive

Deaths

HR

95%CI

p

I

52,1-76,7

89

46

2,35

1,12-4,55

0,01*

II

76,8-85,1

105

29

1,52

0,76-3,02

0,23

III

85,2-94,6

105

29

1,95

1,01-3,76

0,047*

IV

94,7-171,5

118

17

Ref.

Ref.

Ref.

*statistically significant result (p<0.05)

The incidence of death depends on serum selenium concentration in women with breast cancer within 10 years of diagnosis (ranges).

Quartiles

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

< 70

32

28

Ref.

Ref.

Ref.

II

95-102,5

62

2

27,1

6,7-121,2

<0,0001*

*statistically significant result (p<0.05)

The above results are part of the publication by Szwiec M et al., Serum Selenium Level Predicts 10-Years Survival after Breast Cancer; Nutrients 2021, 13(3), 953. [8]

Survival of patients with prostate cancer

Men with prostate cancer and serum selenium concentration in the range of 85-105 µg/l have a significantly reduced risk of death by over 8 times compared to the subgroup with serum selenium concentration below 70 µg/l.

The incidence of death depends on serum selenium concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

≤70

61

33

8,6

3,4-21,7

<0,0001*

II

85-105

95

6

Ref.

Ref.

Ref.

*wynik istotny statystycznie (p <0,05)                                                                                                                                              P.437046

Survival of patients with lung cancer

It has been observed that people whose serum selenium concentration is >67.4 µg/l have a greater chance of longer survival after a lung cancer diagnosis than people with a low serum selenium concentration (<55.1 µg/l).

Frequency of deaths depending on serum selenium concentration in patients with stage I lung cancer within 3 years of diagnosis (tertiles).

Tertiles

Range [µg/l]

total

OR

95%CI

p

I

33,46-57,91

43

2,73

1,21-6,11

0,01*

II

57,92-68,86

42

1,88

0,83-4,28

0,13

III

69,29-108,27

44

Ref.

Ref.

Ref.

*statistically significant result (p<0.05)

The above results are part of the publication by Pietrzak S et al., Influence of the selenium level on overall survival in lung cancer, Journal of Trace Elements in Medicine and Biology 2019, 56:46-51.[9]

Survival of patients with pancreatic cancer

Patients diagnosed with pancreatic cancer have a 3-fold greater chance of 6-month survival if their serum selenium concentration is ≥ 63.67 µg/l compared to patients with selenium concentration below this value.

The incidence of death depends on serum selenium concentration in patients with pancreatic cancer within 6 months of diagnosis (selected ranges).

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

< 63,67

24

33

0,4

0,1-0,97

0,03*

II

≥ 63,67

22

11

Ref.

Ref.

Ref.

The above results are part of the publication by Lener M et al., Serum concentration of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer, Cancer Res Treat., 2016, 48(3):1056-1064.[10]

Survival of patients with melanoma

Patients diagnosed with malignant melanoma have a significantly greater chance of 10-year survival if their serum selenium concentration is higher than 96 µg/l. Patients with serum selenium concentration 96 µg/l.

The incidence of death depends on serum selenium concentration in patients with malignant melanoma within 10 years of diagnosis (quarters).

Quartiles

Range [µg/l]

Alive

Deaths

HR

95%CI

p

I

56,7-76,2

78

16

5,83

1,32-25,8

0,02*

II

76,4-85,01

86

7

3,37

0,7-16,3

0,13

III

85,15-96,06

88

6

3,34

0,67-16,7

0,14

IV

96,15-168

92

2

Ref.

Ref.

Ref.

*statistically significant result (p<0.05)

The above results are the subject of the publication by Rogoża-Janiszewska E. et al., Serum selenium level and the 10-year survival after melanoma, Biomedicines, 2021.[11]

Arsenic and its compounds are among the most recognized toxins. According to the classification of the International Agency for Research on Cancer (IARC), arsenic and its compounds have been categorized as Group 1[12] carcinogens, meaning they are definite human carcinogens. The clinical manifestations resulting from inhalation or ingestion of arsenic compounds vary widely. Depending on the concentration, duration of exposure, and route of absorption, the effects of arsenic interaction with tissues range from relatively benign, such as hypopigmentation, to life-threatening tumors (WHO). Based on existing literature, it can be concluded that not only high but also slightly elevated arsenic concentrations may be linked to cancers, especially in women.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with an arsenic concentration in blood below 0.6 µg/l have a significant, almost 5-fold reduced risk of developing cancers, especially breast cancer, compared to women with an arsenic concentration above 0.6 µg/l (OR=4.7; p=0 .0004; 95%CI:1.9-11.7).

Incidence of breast cancer depending on arsenic concentration in blood (selected ranges)

Group

Range

New cancer diagnosis

Unaffected

OR

95%CI

p

I

<0,6

5

735

Ref.

Ref.

Ref.

II

0,6-0,81

18

723

3,7

1,4-10

0,01*

III

0,82-1,25

21

719

4,3

1,6-11-5

0,002*

IV

>1,25

32

709

6,6

2,6-17,1

<0,0001*

Selected ranges

I

<0,6

5

735

Ref.

Ref.

Ref.

II

≥0,6

71

2222

4,7

1,9-11,7

0,0004*

*wynik istotny statystycznie (p <0,05)  P.425602

The Kaplan-Meier curve for the above correlation is shown below.

-
-

Powyższe wyniki stanowią przedmiot publikacji Marciniak W. et al., Blood arsenic levels and the risk of familial breast cancer in Poland, Int J Cancer, 2020, 146 (10): 2721-2727.[13]

Evaluation of the cancer risk in women - BRCA1 carriers

Women with an arsenic concentration in blood below 0.85 µg/l have a significantly reduced risk of developing cancer by approximately two times compared to women with an arsenic concentration above 0.85 µg/l (OR=2.55; p=0.0006; 95% CI:1.47-4.43).

The incidence of cancer depends on the concentration of arsenic in the blood.

Group

Range

New cancer diagnosis

Unaffected

OR

95%CI

p

I

<0,85

18

513

Ref.

Ref.

Ref.

II

>0,85

49

548

2,55

1,47-4,43

0,0006*

*wynik istotny statystycznie (p<0,05)

The above results are part of the publication by Marciniak W. et al.,  Blood Arsenic Levels as a Marker of Breast Cancer Risk among BRCA1 Carriers, Cancers 2021, 13(13), 3345. [14]

Evaluation of the cancer risk in men

Men whose blood arsenic concentration is between 0.7 and 1.14 µg/l have a nearly 5-fold reduced risk of cancer.

Cancer incidence in men depending on arsenic concentration in blood (selected ranges)

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

0,7-1,14

28

788

Ref.

Ref.

Ref.

II

<0,7 & > 1,14

116

2003

4,8

1,1-2,5

0,03*

*wynik istotny statystycznie (p<0,05) P.437896

 

Survival of patients with prostate cancer

Men with serum arsenic concentration in the range of 0.7-1.0 µg/l have a significantly reduced risk of death by more than 3 times compared to the subgroup with serum arsenic concentration < 0.7 µg/l.

The incidence of death depends on serum arsenic concentration in men with prostate cancer within 5 years of diagnosis (selected ranges).

Group

Range [µg/l]

Deaths

Alive

OR

95%CI

p

I

<0,7

22

50

3,18

1,63-6,22

0,0009*

II

0,7-1,0

22

159

Ref.

Ref.

Ref.

III

>1,0

21

83

1,83

0,95-3,52

0,085

*wynik istotny statystycznie (p<0,05) P.437046

According to the classification of the International Agency for Research on Cancer (IARC), cadmium and its compounds have been categorized as Group 1 [12] human carcinogens. The adverse effects of cadmium and its compounds can lead to kidney diseases, cardiovascular diseases, hypertension, anemia, liver damage, disorders of the reproductive organs, immune system disorders, deficiencies of iron, copper, and zinc, as well as the development of cancer. Numerous studies describe increased levels of cadmium in the biological material of individuals who have developed malignant tumors of the prostate, kidney, bladder, pancreas, and breast.

The literature mentions three main sources of cadmium: diet, smoking, and occupational exposure[25]. The concentration of cadmium in food products is strongly dependent on the content of this element in the environment - air, soil, and water[25]. The concentration of cadmium in the blood is strongly correlated with smoking tobacco products. In non-smokers, Cd concentration is lower compared to smokers[26]. The occupational group most exposed to cadmium are workers in the zinc, steel, and copper industries, as well as in the production of nickel-cadmium batteries, solar cells, and jewelry[27].

Evaluation of the cancer risk in women - BRCA1 non-carriers

The table below shows the distribution of subjects in our chosen range. The risk of cancer is reduced more than 8 times among women whose concentration is in the range of 0.28-0.33 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking women over 50 years of age (selected range)

 

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,28-0,331126Ref.Ref.Ref.
II<0,28 & >0,33446658,341,1-61,10,009*

*wynik istotny statystycznie (p <0,05) P.437608

Evaluation of the cancer risk in women - BRCA1 carriers

In women under 51 years of age with blood cadmium concentration ≤0.32 µg/l, the risk is reduced by more than 8 times compared to women with higher cadmium levels.

Cancer incidence depending on blood cadmium concentration in women under 51 years of age (selected range)

 

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤0,32192Ref.Ref.Ref.
II>0,32222448,301,1-62,460,013*

*wynik istotny statystycznie (p<0,05) PAT.237085

The above results are the subject of a publication sent for publication by Derkacz R. et al., Blood Cadmium Level and the Risk of Cancer in Women with BRCA1 Mutations, Cancers, 2021.[28]

Evaluation of the cancer risk in men

Men who have never smoked cigarettes and whose blood cadmium concentration is below 0.14 µg/l have a nearly 6-fold reduced risk of cancer compared to men with a blood cadmium concentration above 0.28 µg/l.

Cancer incidence depending on blood cadmium concentration in non-smoking men (quarters)

QuartilesRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I0,03-0,144260Ref.Ref.Ref.
II0,14-0,2172571,770,51-6,120,54
III0,21-0,28152493,921,28-11,960,02
IV0,28-2,34212425,641,91-16,670,0004*

*statistically significant result (p<0.05) P.437897

Zinc is an essential element for the proper functioning of the body. It plays a protective role against free radicals, including being part of superoxide dismutase (SOD2). It is also involved in immune processes, contributes to the proper functioning of the skin and mucous membranes, and is involved in storing and secreting insulin from the pancreas. Zinc maintains the ion balance of other trace elements, including selenium, magnesium, and copper, and also plays a detoxifying role with heavy metals. Deficiency of this element leads to serious disorders such as immunodeficiencies, inflammation (including SARS-CoV-2), impaired wound healing, reduced fertility, and vision problems [29,30].

It has been observed that zinc levels change in cancer cells[31]. Normal prostate epithelial cells accumulate zinc, while in cancer cells the level of this element is significantly reduced.[32] Zinc is believed to have anti-cancer effects by inhibiting the growth of cancer cells and activating apoptosis. There are known studies assessing the relationship between zinc concentration and the risk of cancer, but their results are divergent. Some of these studies say that serum zinc concentration is higher in people with cancer [33-35], while others say that the level is lower.[36] The results of research conducted so far also suggest that an appropriate amount of zinc in the diet has a chemopreventive effect. People whose diet is rich in zinc have a lower risk of lung cancer than people following a zinc-poor diet (OR 0.71; 95% CI 0.5-0.99). [37] The risk of colorectal cancer is also lower with a zinc-rich diet (RR 0.86; 95% CI 0.73-1.02).[38] However, zinc supplementation in very high doses above 100 mg/day (the recommended daily intake of zinc is 8 mg/day for women and 12 mg/day for men) has the opposite effect, significantly increasing the risk of prostate cancer (RR 2.29; 95% CI 1.06 – 4.95, p=0.03).[39] The results of research conducted in our Center are presented below.

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women over 50 years of age with a zinc concentration in the blood in the range of 5600-6100 µg/l have a 6.5-fold reduced risk of cancer compared to women with a zinc concentration below 5600 µg/l, and a 3.5-fold reduced risk compared to women with zinc concentration above 6100 µg/l.

Incidence of cancer depending on the concentration of zinc in the blood in non-smoking women over 50 years of age.

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

<5600

20

198

6,5

1-89-22,12

0,0008*

II

5600-6100

3

192

Ref.

Ref.

Ref.

III

>6100

22

399

3,5

1,04-11,94

0,029

*wynik istotny statystycznie (p<0,05) P.437571

Evaluation of the cancer risk in women - BRCA1 carriers

Kobiety z mutacją w genie BRCA1, które nie paliły papierosów mają prawie 3 krotnie obniżone ryzyko zachorowania na raka, jeśli ich poziom cynku znajduje się w zakresie 6000-6700 µg/l. Takiej korelacji nie można stwierdzić wśród osób palących papierosy.

Incidence of cancers depending on the concentration of zinc in the blood in women carriers of mutations in the BRCA1 gene who did not smoke cigarettes (selected ranges)

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

6000-6700

8

218

Ref.

Ref.

Ref.

II

<6000&>6700

49

481

2,8

1,3-6,0

0,006*

*wynik istotny statystycznie (p<0,05)  P.425603

Evaluation of the cancer risk in men

Men who have not smoked cigarettes have a nearly four-fold reduced risk of cancer if their blood zinc concentration is in the range of 5600-6350 µg/l.

Częstość występowania raków w zależności od stężenia cynku we krwi u mężczyzn niepalących (wybrane zakresy)

Quartiles

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

5600-6350

5

318

Ref.

Ref.

Ref.

II

<5600&>6350

41

687

3,8

1,5-9,7

0,0018*

*wynik istotny statystycznie (p<0,05) P.437894

Survival of patients with breast cancer

Women diagnosed with breast cancer and serum zinc concentration > 1000 µg/l have a nearly 6-fold reduced risk of death compared to women with zinc concentration < 700 µg/l.

The table shows the incidence of death according to serum zinc concentration in women with breast cancer (n=538).

Incidence of death depending on serum zinc concentration in women with breast cancer within 10 years of diagnosis (selected ranges)

 

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

≤700

33

25

5,68

2,09-15,42

0,0003*

II

700-850

181

54

2,24

0,91-5,53

0,088

III

851-1000

158

36

1,71

0,68-4,31

0,30

IV

≥1000

45

6

Ref.

Ref.

Ref.

*wynik istotny statystycznie (p<0,05) P.434767

Survival of patients with prostate cancer

Men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200 µg/l have an almost 4-fold reduced risk of death compared to men whose serum zinc concentration is < 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (quarters)

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

≤760,38

56

34

8,4

3,31-21,33

<0,0001*

II

760,39-839,63

75

14

2,58

0,94-7,06

0,095

III

839,64-931,72

78

11

1,95

0,69-5,53

0,31

IV

≥931,73

83

6

Ref.

Ref.

Ref.

*wynik istotny statystycznie (p<0,05) P.437046

Among men diagnosed with prostate cancer whose serum zinc concentration is in the range of 1000-1200, a nearly 4-fold reduced risk of death was observed compared to men whose zinc concentration is lower than 900 µg/l.

Incidence of death depending on serum zinc concentration in men with prostate cancer within 5 years of diagnosis (selected ranges)

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

<900

180

54

3,7

1,09-12,48

0,03*

II

1000-1200

37

3

Ref.

Ref.

Ref.

*wynik istotny statystycznie (p<0,05)  P.437046

The above results are the subject of patent application P.437046.

Survival of patients with laryngeal cancer

Among people with laryngeal cancer, the risk of death was more than twice reduced in patients with zinc concentrations above 688 µg/l in serum compared to those with concentrations <580 µg/l.

Frequency of deaths depending on serum zinc concentration in patients with laryngeal cancer within 5 years of diagnosis (tertiles)

Group

Range [µg/l]

Alive

Deaths

OR

95%CI

p

I

357,76-580,38

52

52

2,45

1,4-4,4

<0,01*

II

584,46-688,89

67

37

1,35

0,8-2,4

0,31

III

688,94-1317,87

76

31

Ref.

Ref.

Ref.

*wynik istotny statystycznie (p<0,05) P.427370

Powyższe wyniki stanowią przedmiot publikacji Lubiński J. et al., Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes, Biomolecules 2021, 11, 865.[40]

Copper performs various functions in the structure of proteins and as a catalyst thanks to the ability to change the degree of oxidation and reduction and occurs in the oxidized (Cu2+) or reduced (Cu+) state. Copper ions can participate in a wide range of interactions with proteins, enabling the formation of complex structures and mediating complex biochemical reactions.[41,42] Copper, like other trace elements, is, on the one hand, essential for the body, but on the other hand, it is very dangerous. . In general, however, conditions that are characterized by general or cell-specific copper accumulation are rare and most often occur as a result of specific genetic disorders.[43]

Evaluation of the cancer risk in women - BRCA1 non-carriers

Non-smoking women under 50 with blood copper concentrations between 850-1000 µg/l have an almost three-fold reduced risk of cancer.

Częstość występowania raków u kobiet niepalących poniżej 50 roku życia, u których nie stwierdzono mutacji w genie BRCA1 (wybrane zakresy).

Group

Range [µg/l]

New cancer diagnosis

Unaffected

OR

95%CI

p

I

850-1000

16

493

Ref.

Ref.

Ref.

II

<850

13

156

2,6

1,2-5,5

0,02*

*statistically significant result (p<0.05) P.438572

Environmental lead contamination is an ongoing problem for developing societies. The toxic effect of lead mainly concerns its effect on the hematopoietic system[44], the peripheral and central nervous system[45] and the gastrointestinal tract[46]. Due to the ubiquity of lead, virtually every person is exposed to contact with this element. Lead toxicity leads, among other things, to changes in the activity of many enzymes and disturbances in the functions of free and structural proteins in the cell[47]. Many studies suggest that an important molecular mechanism of lead toxicity is its participation in the formation of free oxygen radicals, which play a large role in the formation of intracellular damage and in the pathogenesis of many diseases, including malignant tumors[48]. According to the IARC classification of carcinogens, lead and its compounds belong to groups 2a and 2b, i.e. potentially carcinogenic [12].

Evaluation of the cancer risk in women - BRCA1 non-carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by almost 9 times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤81372Ref.Ref.Ref.
II>82610948,841,2-65,410,006*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in women - BRCA1 carriers

Women with blood lead concentration ≤ 8 µg/l have a significantly reduced risk of developing cancer by three times.

Cancer incidence depends on lead concentration in women. (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I≤88217Ref.Ref.Ref.
II>8878122,91,4-6,10,002*

*statistically significant result (p<0.05) P.433150

Evaluation of the cancer risk in men

Men under 60 years of age and non-smokers have an almost 8-fold reduced risk of developing the disease if their lead concentration is lower than 13.5 µg/l.

Cancer incidence depends on lead concentration in non-smoking men under 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I<13,51217Ref.Ref.Ref.
II>13,5164477,81,02-59,00,017*

*statistically significant result (p<0.05) P.437899

Men over 60 years of age, non-smokers have a four-fold reduced risk of cancer if their lead concentration is in the range of 20-50 µg/l in whole blood.

Cancer incidence depends on lead concentration in non-smoking men over 60 years of age (selected ranges).

GroupRange [µg/l]New cancer diagnosisUnaffectedOR95%CIp
I20-50374Ref.Ref.Ref.
II<20 & >5015904,11,1-14,80,02*

*statistically significant result (p<0.05) P.437899

Manganese (Mn) is an essential nutrient involved in properly functioning the immune system, regulation of blood sugar levels and cellular energy, reproduction, digestion, bone growth, blood clotting and homeostasis, and defense against reactive oxygen species. The functions performed by manganese metalloproteins include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [49] Mn acts as a cofactor for various enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase, and Mn superoxide dismutase (Mn-SOD) [50]. Mn tends to accumulate in the liver, pancreas, bones, and brain [50].

The literature contains studies describing the correlation between serum Mn concentration and the risk of breast and colorectal cancer. However, the published studies are retrospective, which makes them unreliable for the conclusion that manganese is a marker of cancer risk. In our Center, we assessed the correlation between manganese concentration and survival of women with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer, whose serum manganese concentration is in the range of 1-10 µg/l, have a significantly reduced risk of death by over 1.5 times compared to other women.

The incidence of death depends on serum manganese concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

Group

Range [µg/l]

Alive

Deaths

HR

95%CI

p

I

1,0-10,0

197

49

Ref.

Ref.

Ref.

II

<1 & > 10

204

87

1,55

1,09-2,20

0,01*

*wynik istotny statystycznie (p<0,05) P.438040

Chromium (Cr) is an element widely distributed in the Earth's crust. This element in small amounts is necessary for the proper functioning of the body, playing a role in the metabolic processes of glucose, some proteins, and fats [51–53]. Increased doses of chromium may have a strong toxic effect, destructively affecting the liver, kidneys, and hematopoietic system, and causing cancer [51,54,55]. Cr(VI) has been found to have a strong mutagenic effect. The results of association studies indicate a relationship between the concentration of chromium in the blood and the risk of cancer in the head, neck, and oral cavity.

In our Center, work was carried out on the correlation between serum chromium concentration and survival of women diagnosed with breast cancer.

Survival of patients with breast cancer

Women diagnosed with breast cancer whose serum chromium concentration is in the range of 0.20-3.5 µg/l have a significantly reduced risk of death by almost two times.

Incidence of death depending on serum chromium concentration in women with breast cancer within 10 years of diagnosis (selected ranges).

Group

Range [µg/l]

Alive

Deaths

HR

95%CI

p

I

0,20-3,5

202

54

Ref.

Ref.

Ref.

II

<0,20 & > 3,5

199

82

1,8

1,28-2,54

0,0002*

*statistically significant result (p<0.05) P.438042

Women who smoke cigarettes and have been diagnosed with breast cancer have a significantly reduced risk of death by almost 4.5 times if their serum chromium concentration is higher than 0.5 µg/l.

Incidence of death depending on serum chromium concentration in smokers with breast cancer within 10 years of diagnosis (selected ranges).

Group

Range [µg/l]

Alive

Deaths

HR

95%CI

p

I

<0,5

157

56

4,46

1,39-14,26

0,01*

II

≥0,5

38

3

Ref.

Ref.

Ref.

*statistically significant result (p<0.05) P.438042

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