Breast cancer is the leading cause of cancer death among Australian women and its incidence is annually increasing. Genetic factors are involved in the complex etiology of breast cancer. The seco-steroid hormone, 1,25 dihydroxy vitamin D 3 can influence breast cancer cell growth in vitro. A number of studies have reported correlations between vitamin D receptor (VDR) gene polymorphisms and several diseases including prostate cancer and osteoporosis. In breast cancer, low vitamin D levels in serum are correlated with disease progression and bone metastases, a situation also noted in prostate cancer and suggesting the involvement of the VDR. In our study, 2 restriction fragment length polymorphisms (RFLP) in the 3ะ region (detected by Apa1 and Taq1) and an initiation codon variant in the 5ะ end of the VDR gene (detected by Fok1) were tested for association with breast cancer risk in 135 females with sporadic breast cancer and 110 cancer-free female controls. Allele frequencies of the 3ะ ApaI polymorphism showed a significant association (p โซุโฌ 0.016; OR โซุโฌ 1.56, 95% CI โซุโฌ 1.09-2.24) while the TaqI RFLP showed a similar trend (p โซุโฌ 0.053; OR โซุโฌ 1.45, 95% CI โซุโฌ 1.00-2.00). Allele frequencies of the FokI polymorphism were not significantly different (p โซุโฌ 0.97; OR โซุโฌ 0.99, 95% CI โซุโฌ 0.69-1.43) in the study population. Our results suggest that specific alleles of the VDR gene located near the 3ะ region may identify an increased risk for breast cancer and justify further investigation of the role of VDR in breast cancer.