Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk

The association between vitamin D receptor (VDR) gene polymorphisms and diseases such as breast cancer, prostate cancer and osteoporosis has been extensively investigated during recent years. To date, several polymorphisms have been found in the VDR gene. In this Finnish case-control study, comprising 483 breast cancer patients and 482 healthy population controls, we investigated the association between altered breast cancer risk and two polymorphisms in the 3' end of the gene detectable with Apal and TaqI restriction enzymes. A statistically significant difference was observed in the Apal genotype distribution between cases and controls. Women with the VDR variant a allele containing genotypes showed a decreased risk for breast cancer [odds ratio (OR) 0.73, 95% confidence interval (Cl) 0.54-0.98] compared to women with the AA genotype. This association was especially strong among women with a positive family history of breast cancer (OR 0.14, 95% Cl 0.03-0.76). Moreover, there was a trend (P for trend = 0.0007) for decreased risk with increasing number of variant alleles. The lowest risk of breast cancer was seen for the women with the aa genotype (OR 0.03, 95% Cl 0.003-0.31) compared to women with the AA genotype. A tendency of decreased risk of breast cancer was also observed for the Taql T allele containing genotypes (Tt and TT) (OR 0.68, 95% Cl 0.41 -1.12), but because the distribution of Taql alleles in the controls missed the Hardy-Weinberg equilibrium (P= 0.01), we were unable to properly assess the potential impact of the TaqI polymorphism in breast cancer susceptibility. In conclusion, our results suggest that the VDR Apal genotype may be an important modifier of individual breast cancer risk among Finnish women, especially if they have a positive family history of breast cancer. Pharmacogenetics 14:239-245 (C) 2004 Lippincott Williams Wilkins