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

Androgens are essential for prostate development, growth and maintenance and the association between androgen levels and prostate cancer is well established. Since the CYP17 gene encodes the enzyme cytochrome P450c17α, which mediates 17α‐hydroxylase and 17,20‐lyase activities in the androgen biosynthesis pathway, sequence variations in the gene and association with increased risk to prostate cancer has been studied. In particular, several groups have studied the association between a polymorphism in the 5′ promoter region and prostate cancer using a population‐based association approach. However, the results from these studies were inconclusive. To further study this polymorphism and its possible role in hereditary prostate cancer (HPC), we performed a genetic linkage analysis and family‐based association analysis in 159 families, each of which contains at least 3 first‐degree relatives with prostate cancer. In addition, we performed a population‐based association analysis to compare the risk of this polymorphism to hereditary and sporadic prostate cancer in 159 HPC probands, 249 sporadic prostate cancer patients and 211 unaffected control subjects. Evidence for linkage 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 did not provide evidence for overtransmission of either allele of the CYP17 polymorphism to affected individuals in the HPC families. The allele and genotype frequencies of the polymorphism were not statistically different among the HPC probands, sporadic cases and unaffected control subjects. In conclusion, our results suggest that the CYP17 gene or other genes in the region may increase the susceptibility to prostate cancer in men; however, the polymorphism in the 5′ promoter region has a minor role if any in increasing prostate cancer susceptibility in our study sample. © 2001 Wiley‐Liss, Inc.