Vitamin D and breast cancer: interaction between dietary vitamin D and genetic variation in the vitamin D receptor may be implicated in the aetiology of breast cancer

The active form of vitamin D has been shown to induce apoptosis and inhibit breast cancer cell growth, mediated by the vitamin D receptor (VDR). Although at least three groups have studied VDR polymorphisms in breast cancer, we are not aware of any published study of interactions. We describe a pilot case-control study. Sixty-five breast cancer cases were recruited through the breast service at Aberdeen Royal Infirmary, Scotland. 58 female controls were selected at random from local general practitioner registers. Subjects completed a food frequency questionnaire and provided a DNA sample (Fok1 and Bsm1 VDR polymorphisms). Women in the highest tertile of vitamin D intake were at two-fold raised risk of breast cancer, compared to the lowest tertile (OR=2.18; 95% CI 0.88-5.39), but this did not reach statistical significance. No association was found between breast cancer risk and the BsmI polymorphism. There was a trend of reducing risk with increasing number of FokI variant alleles; compared to homozygous wild-type, heterozygous women had an almost 30% reduced risk (OR=0.72; 95% CI 0.30-1.70) and homozygous mutants a 60% lower risk (OR=0.40; 95% CI 0.08-1.95). To investigate interactions, subjects were stratified by presence or absence of the FokI variant allele and odds ratios for vitamin D intake computed within each strata. Compared with lowest vitamin D intake levels, higher intake was associated with increased risk in both strata; among women FokI homozygous wild-type OR high vs low=1.90 (0.32-11.31); among Fok1 heterozygotes, OR high vs low=1.50 (0.32-11.31). This finding requires confirmation in other studies.