The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer

The A2 allele of the CYP17 gene has been thought to be associated with incr eased functional activity of this steroidogenic enzyme. Consequently, the A 2 allele has been examined as a biomarker of individual susceptibility to h ormone-related diseases among men and women. We prospectively assessed the association between the A2 allele of CYP27 and prostate cancer risk among 5 90 cases and 782 controls in a case-control study nested within the Physici ans' Health Study cohort. We also evaluated associations between CYP17 geno type and plasma steroid hormones among controls and the potential interacti on between CYP27 and SRD5A2 V89L polymorphisms in relationship with prostat e cancer risk and circulating steroid hormone levels. We observed a borderl ine significant association between the A2 aIlele and prostate cancer risk (odds ratio, 1.23; 95% confidence interval, 0.99-1.54), however, we did not observe evidence of a gene-dosage effect (versus A1/A2 genotype: A1/A2 gen otype; odds ratio, 1.26; 95% confidence interval, 0.99-1.59; A2/A2 genotype : odds ratio, 1.17; 95% confidence interval, 0.85-1.61). The A2 allele was not overrepresented among cases with advanced prostate cancer. Among contro ls, carriers of the A2 allele had steroid hormone levels similar to noncarr iers, We also found no evidence of a gene-gene interaction between CYP27 an d SRD5A2 V89L polymorphisms on prostate cancer risk or endogenous steroid h ormone levels, These results suggest that CYP17 genotype may possibly confe r a small increased susceptibility to prostate cancer but is not a strong p redictor of endogenous steroid hormone levels in men.