Genetic variation in vitamin D-related genes and risk of breast cancer among women of European and East Asian descent

Abstract
Studies of vitamin D-related genetic variants and breast cancer have been inconsistent. This study aimed to investigate associations of vitamin D-related polymorphisms and breast cancer risk among European and East Asian women and potential interactions with menopausal status and breast tumour subtypes. Data from a case-control study of breast cancer (1037 cases and 1050 controls) were used to assess relationships between 21 polymorphisms in two vitamin D-related genes (GC and VDR) and breast cancer risk. Odds ratios were calculated in stratified analyses of European and East Asian women, using logistic regression in an additive genetic model. An interaction term was used to explore modification by menopausal status. Polytomous regression was used to assess heterogeneity by breast tumour subtype. False discovery rate adjustments were conducted to account for multiple testing. No association was observed between GC or VDR polymorphisms and breast cancer risk. Modification of these relationships by menopausal status was observed for select polymorphisms in both Europeans (VDR rs4328262 and rs11168292) and East Asians (GC rs7041 and VDR rs11168287). Heterogeneity by tumour subtype was seen for three VDR polymorphisms (rs1544410, rs7967152 and rs2239186) among Europeans, in which associations with ER-/PR-/HER2+ tumours, but not with other subtypes, were observed. In conclusion, associations between vitamin D-related genetic variants and breast cancer were not observed overall, although the relationships between vitamin D pathway polymorphisms and breast cancer may be modified by menopausal status and breast tumour subtype.