Prostate cancer associated with CYP17 genotype.
Androgens play an important role in the development of prostate cancer. Androgen regulating genes that show allelic variation may be susceptibility factors for the disease. One of these genes, CYP17, encodes the cytochrome P450c17alpha enzyme. It catalyses steroid 17alpha-hydroxylase/17,20 lyase activities at key points in testosterone biosynthesis. We investigated the association between a polymorphism in the CYP17 gene and prostate cancer in a population-based case-control study. All individuals studied were Caucasians born in Sweden, 178 were consecutive clinical prostate cancer patients, and 160 were age-matched control individuals randomly selected from the same catchment area. DNA was extracted from blood samples. A CYP17 gene fragment was amplified by polymerase chain reaction. The MspA1I restriction enzyme, which recognizes the base pair substitution, was used to identify the allelic 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 active androgen synthesizing CYP17 enzyme. Consequently, the CYP17A1/A1 genotype, which was found in a higher frequency among prostate cancer patients, may prove to be one of the important susceptibility factors for prostate cancer. If verified, this genotype is likely to convey a larger risk on a population basis, than the rare hereditary prostate cancer genes do.
Wadelius
M
M
Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden. mia.wadelius@klinfarm.uu.se
Andersson
A O
AO
Johansson
J E
JE
Wadelius
C
C
Rane
E
E
D000368:Aged; D000483:Alleles; D000728:Androgens / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism
D000728:Androgens; D017931:DNA Primers; D013254:Steroid 17-alpha-Hydroxylase