Prostate cancer associated with CYP17 genotype

Androgens play an important role in the development of prostate cancer. And rogen regulating genes that show allelic variation may be susceptibility fa ctors for the disease. One of these genes, CYP17, encodes the cytochrome P4 50c17 alpha enzyme. It catalyses steroid 17 alpha-hydroxylase/17,20 lyase a ctivities at key points in testosterone biosynthesis. We investigated the a ssociation between a polymorphism in the CYP17 gene and prostate cancer in a population-based case-control study. All individuals studied were Caucasi ans born in Sweden, 178 were consecutive clinical prostate cancer patients, and 160 were age-matched control individuals randomly selected from the sa me catchment area. DNA was extracted from blood samples. A CYP17 gene fragm ent was amplified by polymerase chain reaction. The MspA1I restriction enzy me, which recognizes the base pair substitution, was used to identify the a llelic variants CYP17A1 and CYP17A2, Significantly more men homozygous for the CYP17A1 allele were found among prostate cancer patients compared with control individuals; odds ratio 1.61 (95% confidence interval 1.02; 2.53), P = 0.04, According to a preliminary report, the CYP17A1/A1 genotype leads to higher circulating androgen levels, possibly by encoding for a more acti ve androgen synthesizing CYP17 enzyme. Consequently, the CYP17A1/A1 genotyp e, which was found in a higher frequency among prostate cancer patients, ma y prove to be one of the important susceptibility factors for prostate canc er. If verified, this genotype is likely to convey a larger risk on a popul ation basis, than the rare hereditary prostate cancer genes do, Pharmacogen etics 9:635-639 (C) 1999 Lippincott Williams & Wilkins.