Vitamin D receptor polymorphisms (Fokl, Bsml) and breast cancer risk: association replication in two case-control studies within French Canadian population

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nuclectide polymorphisms restriction enzyme detecting SNP of VDR (Fokl and Bsml) with breast cancer risk in two independent case-control studies carried out in the same population. The modifying effect of family history of breast cancer on this relationship was also evaluated. The first and second studies included respectively 718 (255 cases/463 controls) and 1596 (622 cases/974 controls) women recruited in Quebec City, Canada. Fokl and Bsml genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), Fokl ff homozygotes had a higher breast cancer risk (study 1: odds ratio (OR) = 1.22, 95% confidence interval (CI)= 0.76-1.95; study 2: OR = 1.44, 95% CI = 1.05-1.99; and combined studies: OR = 1.33, 950/10 CI = 1.03-1.73). Significant interactions were observed between Foki and family history of breast cancer in the two studies as well as in the combined analysis (P interaction = 0.031, 0.050 and 0.0059 respectively). Among women without family history, odds ratios were 1.00, 1.27 (95% CI = 1.02-1.58) and 1.57 (95% CI = 1.18-2.10) respectively for FF, Ff and ff carriers (P-trend = 0.0013). Bsml Bb + bb genotypes were associated with a weak non-significant increased risk in the two studies (combined OR 1.22, 95% CI = 0.95-1.57) without interaction with family history. Results support the idea that vitamin D, through its signalling pathway, can affect breast cancer risk. They also suggest that variability in observed associations between VDR Fokl and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer