Read-Gene (Poland)

Pathogenic mutations in BRCA1 (BReast CAncer gene 1) confer high risks of both breast (up to 70%) and ovarian (up to 40%) cancers. Zinc (Zn) and copper (Cu) are essential for various physiological functions, including antioxidant reactions. Their balance, reflected in the Zn/Cu ratio, plays a crucial role in maintaining redox homeostasis, which is vital for cancer prevention. This study examines the antioxidant properties of Zn and Cu, specifically focusing on the blood Zn/Cu ratio as a potential marker for cancer risk among BRCA1 mutation carriers. The study cohort consisted of 989 initially unaffected women, followed up for 7.5 years. Blood samples were analyzed using inductively coupled plasma mass spectrometry. Although individual Zn and Cu levels did not significantly correlate with overall cancer risk, those women with a Zn/Cu ratio above 6.38 experienced a significantly lower cancer risk than women with a ratio below this cut-off point. This suggests that the Zn/Cu ratio may be a valuable biomarker for cancer prevention in this high-risk group. Given the increased cancer risk in BRCA1 mutation carriers, optimizing Zn and Cu levels through dietary and active interventions could provide a preventive strategy.

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.

Studies have reported an inverse relationship between serum selenium levels and cancer incidence, but the impact of low serum selenium status on survival after a diagnosis of breast cancer has not been established. We obtained a blood sample from 546 women diagnosed with a first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected after diagnosis, but prior to treatment. Serum selenium was quantified by mass spectroscopy and each patient was assigned to one of four categories (quartiles) based on the distribution in the entire cohort. Patients were followed from diagnosis to death over a mean follow-up of 3.8years. Vital status was obtained by linkage to the Polish National Death Registry. The 5-year overall actuarial survival was 68.1% for women in the lowest (<64.4µg/L) and 82.5% for those in the highest (>81.0µg/L) quartile of serum selenium. In an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53-4.04; P=0.0002) for patients in the lowest quartile of serum selenium, compared to those in all other quartiles. The effect of low selenium on breast cancer-specific mortality was stronger for women who were past smokers (HR 6.03; 95%CI 1.96-18.6; P=0.0002). This study suggests that a selenium level in excess of 64.4µg//L might be beneficial for women undergoing treatment for breast cancer and that selenium supplementation to achieve this level may favorably impact the outcome. Further studies are needed to confirm this association and to evaluate the impact of selenium supplementation on breast cancer survival among women with low post-diagnostic selenium levels.

The study was conducted to determine if serum copper level could be a useful marker for selection for control examinations and if serum copper level is a risk factor in developing cancer. Copper was quantitatively measured in diluted serum samples by inductively coupled plasma mass spectrometry (ICP-MS) using mass spectrometer (Elan DRC-e, PerkinElmer) in standard mode. In our study, there were two independent groups of patients examined. In the first, retrospective model, there were patients diagnosed with prostate cancer (n = 166) and laryngeal cancer (n = 123) matched with healthy controls. This study showed that serum copper level above 1250 µg/l may be a useful marker for laryngeal examination, but is not a useful marker for prostate cancer early detection. In the second, prospective model, there were patents diagnosed with breast cancer (n = 42) matched with unaffected controls. Serum from breast cancer patients was collected 3 - 41 months before cancer diagnosis. This part of study showed that there is a tendency that breast cancer risk is about two times lower when copper serum level is in range between 1035 - 1311 µg/l. Further investigations are needed.

Pancreatic cancer is the eighth most commonly diagnosed cancer in the developed world and has one of the worst prognoses of any malignancy with 98% succumbing to their disease within 5 years. Little is known about the etiology of the disease despite significant new insights into the mutation signatures common to this disease. The antioxidants, including vitamins C, E, Se, Zn might prevent pancreatic cancer. In the current study we have examined the levels of Cu, Fe, Zn and Se in a moderately sized pancreatic cancer population and compared it to a healthy age-matched population.

The aim of the study is identification of correlations between the serum concentrations of iron and the risk of breast cancer among female BRCA1 mutations carriers and unselected breast cancer patients. The first group (99 triplet) selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland (5382insC, C61G, 4153delA). Serum was collected at the time of breast cancer diagnosis. Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria (e.g. age, family cancer history, cigarettes smoking, adnexectomy status ) to achieve the maximum of similarity between them. The subjects of the second group (28 triplet) selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene. Serum was collected 1-2 years before breast cancer diagnosis. One case and two controls were matched for year of birth, past history of cancer, adnexectomy status and cigarettes smoking to achieve the maximum of similarity between them. The subjects of the third group were unselected cancer for the trial were Polish women. Serum was collected during breast cancer diagnosis before treatment. One case and one control were matched for year of birth (+/- 3 years), number and location of cancer among Io relatives, smoking-the number of pack years (+/- 10%), adnexectomy status, CHEK2 mutation. The proportion of cases and control in the first quartile was taken as a reference to calculate the odds ratio, confidence interval and p-value of the multivariate conditional logistic regression. The iron was quantitatively measured by ICP-MS (Inductively Coupled Plasma Mass Spectrometry), (model Elan DRC-e 6100 th, PerkinElmer). This study shows that concentration levels of iron in blood serum are a strong factors associated with an additionally increased risk of breast cancer among BRCA1 mutation carriers and unselected breast cancer patients. For iron concentration in BRCA1 carriers (serum collected at the time of breast cancer diagnosis) all quartiles above the first one had a decreased risk of breast cancer. The results are shown in Table ​Table11. Table 1 Association between Fe serum concentration and risk of breast cancer in BRCA 1 carriers (serum collected at the time of breast cancer diagnosis). For iron concentration in BRCA1 carriers (serum collected 1-2 years before breast cancer diagnosis) the last quartile had a decreased risk of breast cancer. The results are shown in Table ​Table22. Table 2 Association between Fe serum concentration and risk of breast cancer in BRCA 1 carriers (serum collected 1-2 years before breast cancer diagnosis). Individuals classified in the III and IV quartile had lower risk of breast cancer however results were statistically insignificant. The strongest result and lowest cancer risk was for Fe > 1350 μg/l (OR= 0,289, p= 0,0426) For iron concentration in unselected breast cancer patients (serum was collected during breast cancer diagnosis before treatment) all quartiles were statistically insignificant. The results are shown in Table ​Table33. Table 3 Association between Fe serum concentration and risk of breast cancer Individuals classified in the III quartile had lower risk of breast cancer however results were statistically insignificant. The strongest result and lowest cancer risk was for Fe > 1000 μg/l (OR= 0,6698, p= 0,25554). For iron concentration in unselected breast cancer patients (serum was collected during breast cancer diagnosis before treatment) before 55 years old, third quartile had a decreased risk of breast cancer. The results are shown in Table ​Table44. Table 4 Association between Fe serum concentration and risk of cancer in group of patients < 55 years old. Individuals classified in the III quartile had lower risk of breast cancer (OR=0,248, p=0,019); The strongest result and lowest cancer risk was for Fe concentration higher than 987 μg/l (III quartile) ; max 1285 μg/l (III quartile)

Breast cancer belongs to the most common malignancy diagnosed in women. The major inherited susceptibilities to breast cancer are germline mutations in mutations in high risk genes, eg. BRCA1, BRCA2, BRIP, PALB2, RAD51C, RAD51D (5-10%), mutations in moderate risk genes, eg. CHEK2, ATM, NBS1 (10-20%) which however, explain only a small number of breast cancer cases. The latter are alterations in low risk genes and other possible changes in genome, eg. constitutional methylations of BRCA1. Genome – Wide Association Study (GWAS) was thought to help in identification of low risk alleles associated with the risk of particular disease. Up to know 14 GWAS conducted on Caucasian and 6 GWAS on Asian population (http://www.genome.gov/gwastudies/index.cfm?pageid=26525384#searchForm) have been performed on breast cancer cases and 21 variants associated with modest risk of BC (OR <1.3) have been identified. In 2005 have been initiated Breast Cancer Association Consortium (BCAC), an international multidisciplinary forum of investigators interested in the inherited risk of breast cancer. The aim of the consortium is to combine data from many studies in order to identify genes/SNPs and provide a reliable assessment of the breast cancer risks. Currently the BCAC gathers 69 centers from 29 countries, including Poland, and has access to demographic, clinical and epidemiological data from over 76,000 breast cancer patients and 83,000 unaffected women. In GWAS performed by BCAC 14 SNPs have been identified to be associated with modest risks of breast cancer(per-allele ORs<1.3). The aim of this study was to assess usefulness of SNPs identified in BCAC GWAS in diagnostics of breast cancer risk in Polish population. We found that 6 out of 14 SNPs identified in BCAC GWAS were associated with breast cancer risk in Polish patients. Four additional SNPs have been found to be associated with moderate risk of breast cancer in Polish study. Overall, out of 10 SNPs strongest in Polish study 3 seem to be valuable markers for breast cancer diagnostics in Poland: OR 1.91, 95%CI 1.39-2.65, p 0.0001 for carriers of 2 risk alleles and OR 3.2, 95%CI 1.87-5.47, p<0.0001 for carriers of 3 risk allele.