A bstractBreast cancer is the leading cause of cancer death am ong wom en around the world and its incidence is annually increasing. The vitam in D receptor (VDR) gene is a m em ber of the nuclear receptor superfam ily, w hich is expressed in breast tissue and know n to m odulate the rate of cell proliferation. Association betw een the VDR gene polym orphisms and cancer developm ent has been suggested by several studies. How ever, the relationship betw een VDR polym orphism s and breast cancer is controversial and has not been confirm ed by all studies. The purpose of this study w as to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polym orphism s w ith breast cancer in Turkish patients. In this study, 78 patients w ith breast cancer and 27 healthy individuals w ere enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients w ith breast cancer w as sim ilar to that in the norm al population. O ur data indicate that no significant differences exist between the patients and control subjects. Keywords: breast cancer; polymorphism; VDR IntroductionBreast cancer is a heterogeneous disease regarding its morphology, invasive behavior, metastatic capacity, hormone receptor expression and clinical outcome. 10-15% of breast cancer cases have some family history of the disease but only 5% can be explained by rare highly penetrant mutations in genes such as BRCA1 and BRCA2. Although some of the familial risk may be due to the shared environment, there may be other common, low-penetrance genetic variants which alter the predisposition to breast cancer. Endogenous hormone exposure is known to affect breast cancer susceptibility and genes responsive to such hormones are plausible candidates for predisposition genes (Pharoah et al., 1997).The steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) binds the vitamin D receptor (VDR) and the ligand/receptor complex regulates transcription of the genes involved in cell cycle, apoptosis and differentiation (Simboli-Campbell et al., 1996). In the normal mammary gland, 1,25(OH)2D3 may function to regulate calcium transport during lactation or may act in concert with other hormones to maintain mammary cell differentiation and milk protein production (Bhattacharjee et al., 1987;Mezzetti et al., 1988). Dysregulation of VDR-mediated gene expression would alter mammary gland development or function and possibly predispose cells to transformation (Buras et al., 1994).The VDR gene is located on the long arm of chromosome 12 (12q12-14) and is composed of 10 exons, the first of which is not transcribed (Tokita et al., 1996). A series of common polymorphisms in the vitamin D receptor gene were recently reported be associated with both circulating levels of active vitamin D and in vitro measures of gene expression (Morrison et al., 1992). Three of these polymorphisms can be distinguished by digestion with restriction enzymes (Hustmyer et al., 1993). The presence or absence of a restriction site defines the specific all...