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M Sinotte, Departement de medecine sociale et preventive, Universite Laval, Unite de recherche en sante des populations, Centre hospitalier affilie universitaire de Quebec, Quebec, Canada
F Rousseau, Universite Laval, Quebec, Unite de Recherche en Genetique Humaine et Moleculaire, Centre de Recherche de l'Hopital St-Francois-d'Assise du CHUQ, Quebec, Quebec, Canada
P Ayotte, Universite Laval, Quebec, Centre de recherche du Centre Hospitalier Universitaire de Quebec (CHUL), Quebec, Quebec, Canada
E Dewailly, Universite Laval, Quebec, Centre de recherche du Centre Hospitalier Universitaire de Quebec (CHUL), Quebec, Quebec, Canada
C Diorio, McGill University, Montreal, Canada, Breast Cancer Functional Genomics Group and McGill Centre for Bioinformatics, Quebec, Quebec, Canada
Y Giguere, Universite Laval, Quebec, Unite de Recherche en Genetique Humaine et Moleculaire, Centre de Recherche de l'Hopital St-Francois-d'Assise du CHUQ, Quebec, Quebec, Canada
S Berube, Centre hospitalier affilie universitaire de Quebec, Unite de recherche en sante des populations and Centre des maladies du sein Deschenes-Fabia, Quebec, Quebec, Canada
J Brisson, Departement de medecine sociale et preventive, Universite Laval, Unite de recherche en sante des populations and Centre des maladies du sein Deschenes-Fabia, CHA, Quebec, Quebec, Canada

Correspondence: Marc Sinotte, Email: Marc.Sinotte{at}MDDEP.gouv.qc.ca

Abstract

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two VDR gene SNPs (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 relation was also evaluated. The first and second studies included 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 to homozygotes for the F allele (FF genotype), FokI ff homozygotes had a higher breast cancer risk (study 1: OR=1.22, 95%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 (Ptrend=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.