Linkage and association of CYP17 gene in hereditary and sporadic prostate cancer

Androgens are essential for prostate development, growth and maintenance an d the association between androgen levels and prostate cancer is well estab lished. Since the CYP17 gene encodes the enzyme cytochrome P450c 17 alpha, which mediates 17 alpha -hydroxylase and 17,20-lyase activities in the andr ogen biosynthesis pathway, sequence variations in the gene and association with increased risk to prostate cancer has been studied. In particular, sev eral groups have studied the association between a polymorphism in the 5 ' promoter region and prostate cancer using a population-based association ap proach. However, the results from these studies were inconclusive. To furth er study this polymorphism and its possible role in hereditary prostate can cer (HPC), we performed a genetic linkage analysis and family-based associa tion analysis in 159 families, each of which contains at least 3 first-degr ee relatives with prostate cancer. In addition, we performed a population-b ased association analysis to compare the risk of this polymorphism to hered itary and sporadic prostate cancer in 159 HPC probands, 249 sporadic prosta te cancer patients and 211 unaffected control subjects. Evidence for linkag e at the CYP17 gene region was found in the total 159 HPC families (LOD = 1 .3, p = 0.01, at marker D10S222). However, family-based association tests d id not provide evidence for overtransmission of either allele of the CYP17 polymorphism to affected individuals in the HPC families. The allele and ge notype frequencies of the polymorphism were not statistically different amo ng the HPC probands, sporadic cases and unaffected control subjects. In con clusion, our results suggest that the CYP17 gene or other genes in the regi on may increase the susceptibility to prostate cancer in men; however, the polymorphism in the 5 ' promoter region has a minor role If any in increasi ng prostate cancer susceptibility in our study sample.(C) 2001 Wiley-Liss, Inc.