Weight status and alcohol intake modify the association between vitamin D and breast cancer risk

Abstract

Background: Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors. Objective: Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m2) and alcohol intake. Methods: A nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU. VI.MAX) cohort (1994-2007), involving 233womenwith breast cancer and 466matched controls (mean± SD age: 496 ± y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed. Results: A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < 10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D. Conclusion: In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428.