Association of a vitamin D receptor polymorphism with sporadic breast cancer development

Breast cancer is the leading cause of cancer death among Australian women a nd its incidence is annually increasing. Genetic factors are involved in th e complex etiology of breast cancer. The seco-steroid hormone, 1,25 dihydro xy vitamin D-3 can influence breast cancer cell growth in vitro. A number o f studies have reported correlations between vitamin D receptor (VDR) gene polymorphisms and several diseases including prostate cancer and osteoporos is. In breast cancer, low vitamin D levels in serum are correlated with dis ease progression and bone metastases, a situation also noted in prostate ca ncer and suggesting the involvement of the VDR. In our study, 2 restriction fragment length polymorphisms (RFLP) in the 3' region (detected by ApaI an d TaqI) and an initiation codon variant in the 5' end of the VDR gene (dete cted by FokI) were tested for association with breast cancer risk in 135 fe males with sporadic breast cancer and 110 cancer-free female controls. Alle le frequencies of the 3' ApaI polymorphism showed a significant association (p = 0.016; OR = 1.56, 95% CI = 1.09-2.24) while the TaqI RFLP showed a si milar trend (p = 0.053; OR = 1.45, 95% CI = 1.00-2.00). Allele frequencies of the FokI polymorphism were not significantly different (p = 0.97; OR = 0 .99, 95% CI = 0.69-1.43) in the study population. Our results suggest that specific alleles of the VDR gene located near the 3' region may identify an increased risk for breast cancer and justify further investigation of the role of VDR in breast. (C) 1999 Wiley-Liss, Inc.