Zinc and Its Antioxidant Properties: The Potential Use of Blood Zinc Levels as a Marker of Cancer Risk in BRCA1 Mutation Carriers.

BRCA1 mutations predispose women to breast and ovarian cancer. The anticancer effect of zinc is typically linked to its antioxidant abilities and protecting cells against oxidative stress. Zinc regulates key processes in cancer development, including DNA repair, gene expression, and apoptosis. We took a blood sample from 989 female BRCA1 mutation carriers who were initially unaffected by cancer and followed them for a mean of 7.5 years thereafter. There were 172 incident cases of cancer, including 121 cases of breast cancer, 29 cases of ovarian cancers, and 22 cancers at other sites. A zinc level in the lowest tertile was associated with a modestly higher risk of ovarian cancer compared to women with zinc levels in the upper two tertiles (HR = 1.65; 95% CI 0.80 to 3.44; p = 0.18), but this was not significant. Among those women with zinc levels in the lowest tertile, the 10-year cumulative risk of ovarian cancer was 6.1%. Among those in the top two tertiles of zinc level, the ten-year cumulative risk of ovarian cancer was 4.7%. There was no significant association between zinc level and breast cancer risk. Our preliminary study does not support an association between serum zinc level and cancer risk in BRCA1 mutation carriers.

Selenium and Arsenic Levels, Prevalence of Common Variants of Genes Involved in Their Metabolism, and Psoriasis Disease.

Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped 336 patients and 903 matched controls to evaluate the prevalence of SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) polymorphisms using Taqman assays. The mean selenium (Se) level in serum was 74 µg/L in patients and 86 µg/L in controls (p < 0.001). The mean Se level in blood was 95 µg/L in patients and 111 µg/L in controls (p < 0.001). Psoriasis risk was greatest among participants with the lowest serum (<68.75 µg/L, OR: 8.30; p < 0.001) and lowest blood concentrations of Se (<88.04 µg/L, OR: 10.3; p < 0.001). Similar results were observed in subgroups of males and females. We found an inverse correlation of selenium levels with PASI, NAPSI, and BSA scores. There was no significant difference in the distribution of the CAT, GPX1, DMGDH, and SOD2 polymorphisms. Among carriers of rs4880, rs1001179, and rs921943 polymorphisms, blood selenium levels were significantly lower. The mean arsenic level in serum was 0.79 µg/L in patients and 0.7 µg/L in controls (p = 0.2). The mean concentration in blood was 1.1 µg/L in patients and 1.3 µg/L in controls (p < 0.001). In conclusion, we found that lower selenium levels, in blood and serum, are associated with psoriasis risk and its more severe course. Future prospective studies should focus on the optimalisation of the concentration of this trace element not only for prophylactic guidance but also to support the treatment of this disease.

Blood Cadmium Level Is a Marker of Cancer Risk in Men.

Cadmium (Cd) is a known carcinogen, but its impact on cancer risk at lower concentrations is poorly understood. Previous studies on Cd and cancer risk in men show inconsistent results, prompting further investigation. A prospective cohort study involving 2956 men was conducted. Blood Cd levels were measured, and participants were followed for 78 months to assess cancer incidence. Men with high blood Cd levels (>0.71 µg/L) had a significantly increased risk of cancer compared to those with low levels (<0.19 µg/L) (HR 3.42, p < 0.001), particularly among non-smokers (HR 3.74, p = 0.003), individuals aged < 60 years (HR 2.79, p = 0.017), and ≥60 (HR 4.63, p = 0.004). The influence of smoking on cancer risk based on Cd levels was not significant in this study. Blood Cd levels may influence cancer risk in men, emphasizing the importance of minimizing Cd exposure to reduce risk. Confirmation of these results in other populations is essential for effective preventive measures against Cd-related cancers.

Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers.

BRCA1 mutations substantially elevate the risks of breast and ovarian cancer. Various modifiers, including environmental factors, can influence cancer risk. Lead, a known carcinogen, has been associated with various cancers, but its impact on BRCA1 carriers remains unexplored. A cohort of 989 BRCA1 mutation carriers underwent genetic testing at the Pomeranian Medical University, Poland. Blood lead levels were measured using inductively coupled plasma mass spectrometry. Each subject was assigned to a category based on their tertile of blood lead. Cox regression analysis was used to assess cancer risk associations. Elevated blood lead levels (>13.6 µg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23-9.00; p = 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01; p = 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.

Serum Levels of Copper and Zinc and Survival in Breast Cancer Patients.

There is emerging interest in the relationship between several serum micronutrients and the prognosis of patients with breast cancer. The relationship between serum zinc and copper levels and breast cancer prognosis is unclear. In our study, we included 583 patients with breast cancer diagnosed between 2008 and 2015 in the region of Szczecin, Poland. In a blood sample obtained before treatment, serum zinc and copper levels were quantified by mass spectroscopy. Each patient was assigned to one of four categories (quartiles) based on the distribution of the elements in the entire cohort. Patients were followed from diagnosis to death over a mean of 10.0 years. The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio (p < 0.001). The multivariate hazard ratio (HR) for breast cancer death was 2.07 (95% CI 1.17-3.63; p = 0.01) for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific survival after breast cancer diagnosis.

Correlation between Selenium and Zinc Levels and Survival among Prostate Cancer Patients.

The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.

An Assessment of Serum Selenium Concentration in Women with Ovarian Cancer.

BACKGROUND: Available studies on the effect of serum selenium levels on the risk of malignancies show some conflicting results. In this study, we investigated the correlation between serum selenium levels and ovarian cancer occurrence. METHODS: 314 women (157 diseased patients and 157 healthy ones) matched in terms of age and BMI were included in the study. The measurements of selenium in the collected blood samples were performed using an ICP mass spectrometer. Univariable and multivariable analyzes were performed to determine the relationship between the factors under the study and the occurrence of ovarian cancer. RESULTS: The mean concentration of selenium was lower among diseased ones than among controls (53.31 µg/L vs. 78.99 µg/L). A decrease in selenium concentration was noticed with the advancement of ovarian cancer. In univariable and multivariable analyzes, a clear relationship between low selenium concentration and the occurrence of ovarian cancer was found (35.3 (95% CI: 11.2-111; p < 0.001) and 45.8 (95% CI: 12.8-164; p < 0.001)). CONCLUSION: The studied patients with ovarian cancer are characterized by statistically significant lower serum selenium levels than patients from the control group. Among the study group, a decrease in selenium concentration was observed with an increase in the FIGO stage. The determination of the role of selenium as a prophylactic factor in ovarian cancer requires further prospective studies.

Study of Serum Copper and Zinc Levels and Serum Cu/Zn Ratio among Polish Women with Endometrial Cancer.

BACKGROUND: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. METHODS: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. RESULTS: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 µg/L vs. 1176.42 µg/L, p < 0.001; Zn: 707.05 µg/L vs. 901.67 µg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). CONCLUSION: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

Serum Iron Level and 10-Year Survival after Melanoma.

The malignant melanoma of the skin is a very aggressive tumor. The determination of prognostic biomarkers is important for the early detection of recurrence, and for the enrollment of the patients into different treatment regimens. An evaluation of a cohort of 375 Polish MM cases revealed that a low serum iron concentration (i.e., below 893.05 µg/L) was associated with increased mortality. The study group was followed up from the date of melanoma diagnosis until death or 2020. Patients were assigned to one of four categories in accordance with increasing iron level (I-IV quarters). Patients with a low iron level of below 893.05 µg/L (I quarter) had a significantly lower survival rate when compared to the subgroup with the highest iron level, above 1348.63 µg/L (IV quarter; HR = 4.12; p = 0.028 and HR = 4.66; p = 0.019 for uni- and multivariable models, respectively). Multivariable analysis took into account the following factors: iron levels, Clark, sex, and age. Future studies based upon the examination of a larger number of cases should be conducted to confirm our findings.

Evaluation of Physiotherapy Impact on Neuromuscular Tension in Analog Astronauts at the LunAres Habitat.

The evaluation of manual Trigger Point Therapy (TrPt) on mandible abduction range of Analog Astronauts (AA) surviving isolation conditions during consecutive missions at the LunAres Habitat was performed. This physiotherapy method was applied to decrease stress-related neuromuscular tension. Abduction measurements were conducted on the two groups of five AA, who endured severe isolation conditions for 14 days in the limited space of the LunAres Research Station Habitat (Pila, Poland) during missions. The test group consisted of abduction measurements of AA who received TrPt and control group of abduction measurements of AA who did not receive TrPt. All measurements were noted in the TemporoMandibular Joint (TMJ) diagnosis aspect of the integrated dental examination card SZOPPDP©. The ischemic compression was performed on an active localized trigger point-resulting in cessation of pain. Maximum abduction measurements were made with an electronic caliper, and the abduction range was compared. The change of abduction range in AA with TrPt was bigger than in AA without TrPt. A larger increase in abduction range was observed in every case in the group receiving TrPt compared to the control group. TrPt effectively decreases the neuromuscular tension, which results in an increased mandibular abduction range of AA. Observations conducted in LunAres Research Station regarding stress-related neuromuscular tension can help identify effective therapeutic methods for circumstances of social isolation.

An Assessment of Serum Selenium Concentration in Women with Endometrial Cancer.

Background: Numerous studies have shown a relationship between low serum selenium levels and an increased risk of developing cancer. Methods: A total of 306 women participated in the study: 153 patients diagnosed with endometrial cancer and 153 healthy women who were matched, in terms of birth year (+/−3 years), to the patients from the study group. The quantitative measurement of selenium content in the collected blood samples was performed using a mass spectrometer with excitation in inductively coupled plasma. In order to determine the relationship between the risk factors and the incidence of endometrial cancer, analyses based on single- and multi-factor conditional logistic regression models were performed. Results: The mean concentration of selenium was lower in patients with endometrial cancer than in healthy controls (60.63 µg/L (0.77 µmol/L) vs. 78.74 µg/L (0.99 µmol/L), respectively). When compared in quartiles, a significant association of lower selenium concentration with the incidence of endometrial cancer was recorded. The highest OR was observed in the first and second quartiles (OR-22.0, p-value < 0.001; medium selenium level 46.95 µg/L (0.59 µmol/L), and OR-5.94; p-value < 0.001; medium selenium level 63.60 µg/L (0.80 µmol/L), respectively). Conclusion: A strong correlation between the level of selenium in the blood serum and the risk of endometrial cancer indicates that patients with low levels should be a candidate group requiring appropriate preventive examinations. Further research on a larger group of patients is required.

Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor.

BACKGROUND: There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs. METHODS: The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated. RESULTS: The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01). CONCLUSIONS: Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.

An Assessment of GPX1 (rs1050450), DIO2 (rs225014) and SEPP1 (rs7579) Gene Polymorphisms in Women with Endometrial Cancer.

BACKGROUND: Numerous studies indicate a relationship between the presence of GPX1 (rs1050450), DIO2 (rs225014) and SEPP1 (rs7579) gene polymorphisms and the development of chronic or neoplastic diseases. However, there are no reports on the influence of these polymorphisms on the development of endometrial cancer. METHODS: 543 women participated in the study. The study group consisted of 269 patients with diagnosed endometrial cancer. The control group consisted of 274 healthy women. Blood samples were drawn from all the participants. The PCR-RFLP method was used to determine polymorphisms in the DIO2 (rs225014) and GPX1 (rs1050450) genes. The analysis of polymorphisms in the SEPP1 (rs7579) gene was performed by means of TaqMan probes. RESULTS: There was a 1.99-fold higher risk of developing endometrial cancer in CC homozygotes, DIO2 (rs225014) polymorphism (95% Cl 1.14-3.53, p = 0.017), compared to TT homozygotes. There was no correlation between the occurrence of GPX1 (rs1050450) and SEPP1 (rs7579) polymorphisms and endometrial cancer. CONCLUSION: Carriers of the DIO2 (rs225014) polymorphism may be predisposed to the development of endometrial cancer. Further research confirming this relationship is recommended.

Risk of Second Primary Thyroid Cancer in Women with Breast Cancer.

The goal of this study was to estimate the risk of thyroid cancer following breast cancer and to identify therapeutic and genetic risk factors for the development of thyroid cancer after breast cancer. We followed 10,832 breast cancer patients for a mean of 14 years for new cases of thyroid cancer. All women were genotyped for three Polish founder mutations in BRCA1 (C61G, 4153delA, 5382insC) and four mutations in CHEK2 (1100delC, IVS2 + 1G/A, del5395, I157T). Information was collected on chemotherapy, radiotherapy, hormonal therapies, and oophorectomy. Of the 10,832 women, 53 (0.49%) developed a second primary thyroid cancer. Based on Polish population statistics, the expected number was 12.4 (SIR = 4.3). The ten-year risk of developing thyroid cancer was higher in women who carried a CHEK2 mutation (1.5%) than in women who carried no mutation (0.9%). The age-adjusted hazard ratio for developing thyroid cancer was 1.89 (0.46-7.79; p = 0.38) for those with a CHEK2 protein-truncating mutation and 2.75 (1.29-5.85; p = 0.009) for those with a CHEK2 missense mutation.

Blood Copper Levels and the Occurrence of Colorectal Cancer in Poland.

There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls. Cases and controls were matched for sex, smoking status (yes/no) and year of birth. Among the cases, the mean blood copper level was 1031 µg/L (range 657 µg/L to 2043 µg/L) and among the controls, the mean blood copper level was 864 µg/L (range 589 µg/L to 1433 µg/L). The odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98-32.3; p < 0.001). Of the patients with stage I-II colon cancer, 62% had a copper level in the highest quartile. A blood copper level in excess of 930 µg/L is associated with an increase in the prevalence of colorectal cancer in the Polish population and its potential use in early detection programs should be considered.

Low Blood-As Levels and Selected Genotypes Appears to Be Promising Biomarkers for Occurrence of Colorectal Cancer in Women.

In following study we examined whether blood arsenic (As) levels combined with specific polymorphisms in MT1B, GSTP1, ABCB1, NQO1, CRTC3, GPX1, SOD2, CAT, XRCC1, ERCC2 can be used as a marker for the detection of colorectal cancer (CRC) among Polish women. A retrospective case-control study of CRC included 83 CRC cases and 78 healthy controls. From each study participant pre-treatment peripheral blood was collected for As level measurement by inductively coupled-plasma mass spectrometry (ICP-MS). We estimated the odds ratio (OR) of the association between blood-As levels and CRC using multivariable unconditional logistic regression models. A low blood-As level (0.27-0.67 µg/L) was associated with an increased frequency of CRC (OR: 3.69; p = 0.005). This correlation was significantly greater when participants carried particular gene variants: CAT, rs1001179-nonCC (OR: 19.4; p = 0.001); ABCB1 rs2032582-CC (OR: 14.8; p = 0.024); GPX1 rs1050450-CC (OR: 11.6; p = 0.002) and CRTC3 rs12915189-nonGG (OR: 10.3; p = 0.003). Our study provides strong evidence that low blood-As levels are significantly associated with increased CRC occurrence and that particular gene variants significantly enhanced this correlation however, due to the novelty of these findings, we suggest further validation before a definitive statement that the combined effect of low blood-As levels with specific gene polymorphisms is a suitable CRC biomarker.

Influence of the Levels of Arsenic, Cadmium, Mercury and Lead on Overall Survival in Lung Cancer.

The effects of heavy metals on cancer risk have been widely studied in recent decades, but there is limited data on the effects of these elements on cancer survival. In this research, we examined whether blood concentrations of the heavy metals arsenic, cadmium, mercury and lead were associated with the overall survival of lung cancer patients. The study group consisted of 336 patients with lung cancer who were prospectively observed. Blood concentrations of heavy metals were measured to study the relationship between their levels and overall survival using Cox proportional hazards analysis. The hazard ratio of death from all causes was 0.99 (p = 0.94) for arsenic, 1.37 (p = 0.15) for cadmium, 1.55 (p = 0.04) for mercury, and 1.18 (p = 0.47) for lead in patients from the lowest concentration quartile, compared with those in the highest quartile. Among the patients with stage IA disease, this relationship was statistically significant (HR = 7.36; p < 0.01) for cadmium levels in the highest quartile (>1.97-7.77 µg/L) compared to quartile I (0.23-0.57 µg/L, reference). This study revealed that low blood cadmium levels <1.47 µg/L are probably associated with improved overall survival in treated patients with stage IA disease.

Serum Selenium Level and 10-Year Survival after Melanoma.

Melanoma is one of the most aggressive human malignancies. The determination of prognostic biomarkers is important for the early detection of recurrence and for the enrollment of the patients into different treatment regimens. Herein, we report the 10-year survival of 375 melanoma patients depending on their serum selenium levels. The study group was followed up from the date of melanoma diagnosis until death or 2020. Patients were assigned to one of four categories, in accordance with the increasing selenium level (I-IV quartiles). The subgroup with low selenium levels had a significant lower survival rate in relation to patients with high selenium levels, HR = 8.42; p = 0.005 and HR = 5.83; p = 0.02, for uni- and multivariable models, respectively. In the univariable analysis, we also confirmed the association between Breslow thickness, Clark classification and age at melanoma prognosis. In conclusion, a low serum selenium level was associated with an increased mortality rate in the 10 years following melanoma diagnosis. Future studies in other geographic regions with low soil selenium levels should be conducted to confirm our findings.

Blood Arsenic Levels as a Marker of Breast Cancer Risk among BRCA1 Carriers.

An important group of breast cancers is those associated with inherited susceptibility. In women, several predisposing mutations in genes involved in DNA repair have been discovered. Women with a germline pathogenic variant in BRCA1 have a lifetime cancer risk of 70%. As part of a larger prospective study on heavy metals, our aim was to investigate if blood arsenic levels are associated with breast cancer risk among women with inherited BRCA1 mutations. A total of 1084 participants with pathogenic variants in BRCA1 were enrolled in this study. Subjects were followed from 2011 to 2020 (mean follow-up time: 3.75 years). During that time, 90 cancers were diagnosed, including 67 breast and 10 ovarian cancers. The group was stratified into two categories (lower and higher blood As levels), divided at the median (<0.85 µg/L and ≥0.85 µg/L) As level among all unaffected participants. Cox proportional hazards models were used to model the association between As levels and cancer incidence. A high blood As level (≥0.85 µg/L) was associated with a significantly increased risk of developing breast cancer (HR = 2.05; 95%CI: 1.18-3.56; p = 0.01) and of any cancer (HR = 1.73; 95%CI: 1.09-2.74; p = 0.02). These findings suggest a possible role of environmental arsenic in the development of cancers among women with germline pathogenic variants in BRCA1.

Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes.

Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes. The study group consisted of 300 patients treated surgically for laryngeal cancer. Serum zinc levels and common polymorphisms in SOD2, CAT and GPX1 were analyzed. The risk of death in patients with the lowest zinc levels was increased in comparison with patients with the highest levels. Polymorphisms of antioxidant genes by themselves were not correlated with survival, however, serum zinc level impact on survival was stronger for SOD2 TC/TT and CAT CC variants. GPX1 polymorphisms did not correlate with zinc levels regarding survival. In conclusion, serum zinc concentration appears to be an important prognostic factor for survival of patients diagnosed with laryngeal cancer. When higher zinc levels were correlated with polymorphisms in SOD2 and CAT a further increase in survival was observed.