Combined Effects of Selenium, Arsenic, and CAT rs1001179 Genotype on Cancer Risk in Women with Familial Breast Cancer Predisposition

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(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.

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