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.

Background/Objectives: To correlate blood lead (Pb) levels with cancer risk in a prospective cohort of healthy women with non-occupational exposure to lead. We hypothesize that blood Pb levels can predict the risk of cancer in healthy women. Methods: The study was performed with women registered at the Hereditary Cancer Centre, Szczecin, aged 40 years and above between September 2010 and March 2024. A total of 2927 unaffected women were included in the study. Exclusion criteria were BRCA1 gene mutation, women with diagnosed cancer, and women with occupational exposures to Pb. All patients were asked about their occupational exposure and tested for the three Polish BRCA1 founder mutations (c.5266dupC/5382insC; c.181T > G/300T > G; c.4035delA/4153delA). Inductively coupled plasma mass spectrometry was used to measure blood Pb levels. The study was blinded to all scientists involved, and all samples were assayed in the absence of any knowledge about the clinical status of each participant. Results: There were 239 incident cancers diagnosed in the cohort after an average follow-up of 6 years. Compared to women with the lowest blood Pb concentration, women with higher blood Pb levels had a significantly increased risk of developing any cancer (HR = 1.46; (95% CI: 1.006–2.13; p = 0.046)). The association was stronger for women below the age of 50 years at study entry (HR = 2.59; (95% CI: 1.37–4.89; p = 0.003)). For women over 50 years of age, the results were statistically insignificant. Conclusions: This study suggests that blood Pb levels have the potential to be used as a marker of cancer risk in women under 50 years of age who have no known occupational exposure to this heavy metal. Further investigations using additional groups of women from Poland and other countries are needed for validate these findings.

(1) Background: Selenium (Se) and arsenic (As) influence oxidative stress pathways and may jointly affect cancer risk. We investigated whether Se and As status, individually and in combination, are associated with cancer incidence in women with familial breast cancer predisposition. (2) Methods: In this multicenter prospective study, 6134 BRCA1-negative women aged ≥40 years with hereditary breast cancer predisposition were recruited from 16 genetic clinics in Poland. Blood Se and As concentrations were measured repeatedly during follow-up (6–60 months). Primary analyses evaluated cancer risk across combined Se and As strata within a predefined optimal Se range (98–108 µg/L), including analyses stratified by CAT rs1001179 genotype. Exploratory analyses assessed a composite Risk Index (RI = Se + As × 50). Associations with incident cancer were examined using multivariable Cox regression models. (3) Results: Among 6134 participants, 4847 (79.0%) completed follow-up. The lowest cancer risk was observed in women with Se concentrations of 98–108 µg/L and As concentrations of 0.57–0.75 µg/L. Compared with women with As concentrations >1.07 µg/L, this subgroup showed a lower cancer hazard (HR 3.46; 95% CI 1.28–9.32). Associations were stronger when Se, As, and CAT genotype were analyzed jointly (HR 4.74; 95% CI 1.44–15.53). The RI was also associated with cancer risk (HR 4.51; 95% CI 1.72–11.83). (4) Conclusions: Cancer risk varied according to combined selenium and arsenic status. Stronger associations observed after CAT stratification support a potential role for oxidative stress–related gene–environment interactions in cancer susceptibility.

The aim of this study was to investigate whether genotypes of HRG may modify the effect of Se(selenium) on all-cause mortality and cancer risk. The study was conducted on 2782 initially unaffected women from families with familial breast cancers, all registered at the Hereditary Cancer Centre in Szczecin. Participants were aged 40 years or older and were recruited between September 2010 and March 2024. Women carrying a BRCA1 mutation and those with a diagnosed cancer were excluded from the study. Blood Se levels were measured using inductively coupled plasma mass spectrometry, and molecular analyses of HRG (Histidine-rich glycoprotein) genotypes were performed using real-time PCR with TaqMan probes. After an average follow-up period of 6 years and 2 months, 89 deaths and 210 cases of cancer were identified. The study showed significant differences in the reference range of blood selenium levels, as well as its impact on all-cause mortality and cancer risk, depending on HRG genotype. The most striking finding regarding all-cause mortality risk was observed among women over 50 years of age, effect estimates are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). Regardless of genotype, women with blood selenium (Se) levels in the lowest quartile (Q1) had a significantly higher all-cause mortality risk compared with those in the highest quartile (Q4), (HR = 3.07; 95%CI: 1.53–6.16; p = 0.001). Among women with the HRG non-TT genotype, the risk was even more pronounced—those with Se levels in Q1 had a significantly increased mortality risk compared with women in the higher quartiles (Q2–Q4) (HR = 7.68; 95%CI: 2.31–25.47; p = 0.0008). In contrast, for carriers of the HRG TT genotype, increased all-cause mortality risk was observed only when blood Se levels were in Q1 compared with Q4 (HR = 2.40; 95%CI: 1.09–5.31; p = 0.029). Important findings for any cancer risk have emerged in women below 50 years of age. Among women with the HRG TT genotype, the cancer risk was significantly increased in Q1 compared with women in Q2 (HR = 4.15; 95%CI: 1.55–11.06; p = 0.004). In contrast, the results for HRG non-TT carriers, regardless of genotype, were statistically insignificant. In summary, mortality and cancer risk appeared to be dependent on HRG genotype and blood Se levels.

This study’s aim was to clarify the regulatory roles of the MKI67 rs11016073 and APOB rs1367117 polymorphisms in the relationship between blood Pb levels and cancer risk. Blood Pb concentrations were measured using inductively coupled plasma mass spectrometry, and genotyping was performed by real-time PCR with TaqMan probes. Cancer incidence was assessed during a mean follow-up of six years and two months. During follow-up, 210 incident cancers were diagnosed among 2782 women. Pb exposure was categorized into quartiles (Q1: 17.16 µg µg/L). The association between Pb levels and cancer risk was strongly genotype dependent. Women carrying APOB non-GG and MKI67 non-AA genotypes exhibited the lowest breast cancer risk at the highest Pb levels (Q4), whereas carriers of APOB GG and MKI67 AA showed the lowest risk at the lowest Pb levels (Q1). Age-stratified analyses further demonstrated genotype-specific differences in optimal Pb exposure ranges, particularly for breast cancer. Cancer risk associated with Pb exposure is not uniform but depends on genetic background. These findings identify genotype-specific optimal blood Pb levels and suggest that incorporation of MKI67 and APOB genotyping may improve risk stratification and interpretation of non-linear Pb–cancer associations.