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¹ Unité de Recherche en Santé des Populations, Centre Hospitalier Affilié Universitaire de Québec, 1050 Chemin Sainte-Foy, Québec, Québec, Canada G1S 4L8² , Département de Médecine Sociale et Préventive³ Unité de Recherche en Génétique Humaine et Moléculaire, Centre de Recherche de l'Hôpital St-François-d'Assise du CHUQ, Université Laval, Québec, Canada G1V 0A6⁴ Unité de Recherche en Santé Publique, Centre de Recherche du Centre Hospitalier Universitaire de Québec (CHUL), Québec, Canada⁵ Centre des Maladies du Sein Deschênes-Fabia, Centre Hospitalier Affilié Universitaire de Québec, 1050 Chemin Sainte-Foy, Québec, Québec, Canada G1S 4L8⁶ Breast Cancer Functional Genomics Group and McGill Centre for Bioinformatics, McGill University, Montréal, Canada

(Correspondence should be addressed to J Brisson; Email: jacques.brisson{at}uresp.ulaval.ca)

This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms restriction enzyme detecting SNP of VDR (FokI and BsmI) 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. FokI and BsmI genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), FokI 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, 95% 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). BsmI 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 FokI and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer.