Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among women living in the southwestern U.S.

Population-based case-control study of women aged 24–79 years in Colorado, New Mexico, Utah, and selected counties of Arizona; self-identified NHW or Hispanic; first primary breast cancer cases diagnosed 1999–2004; population-based controls frequency-matched by 5-year age groups; data collected via in-person interviews; dietary vitamin D intake assessed by FFQ; VDR genotyping performed (BsmI, FokI, Poly A).

Vitamin D supplementation: 10+ µg/day (400+ IU) taken orally, during the referent period (1 year prior to diagnosis).

Higher dietary vitamin D intake was positively associated with breast cancer (Q4 vs Q1: OR 1.35; 95% CI 1.15–1.60; Ptrend 0.003). Vitamin D supplement use (≥10 µg/day) was inversely associated with breast cancer (OR 0.79; 95% CI 0.65–0.96; Ptrend 0.01). Associations were observed in both NHW and Hispanic women and varied by hormone receptor status: dietary vitamin D linked to ER+/PR+ and ER−/PR− cancers; supplementation inversely linked to ER+/PR+ and ER−/PR− cancers; no clear effect for ER+/PR−. VDR genotypes did not have a main effect, but interactions with dietary vitamin D were found for BsmI, Poly A, and FokI genotypes. Authors call for further research to clarify differences by vitamin D source and hormone receptor status; results may be influenced by residual confounding and exposure misclassification; no causal claims.

Observational case-control design; potential recall bias and exposure misclassification for dietary vitamin D and supplements; residual confounding; possible selection bias due to participation rates; limited generalizability to NHW and Hispanic women in the US Southwest; small numbers in some genotype subgroups; multiple subgroup analyses increase risk of chance findings; potential survival bias due to timing of interviews after diagnosis.