Association of the polymorphisms of genes involved in androgen metabolism and signaling pathways with familial prostate cancer risk in a Japanese population.
BACKGROUND
Androgen plays a central role in the normal and malignant development of prostate glands. Genetic polymorphisms of genes involved in androgen metabolism and signaling might be associated with the risk of prostate cancer.


METHODS
One hundred and two patients with prostate cancer with a family history and 117 healthy age- and residence-matched male controls were enrolled. Genotypes of the CAG repeat length of androgen receptor (AR), CYP17, 5alpha-reductase type II (SRD5A2), UDG-glucuronosyltransferase (UGT) 2B15, PSA promoter genes were analyzed.


RESULTS
For single polymorphisms, the presence of Y alleles showed a significantly lower risk of prostate cancer in comparison with the D/D genotype in UGT2B15 (odds ratio [OR]=0.41, 95% confidence interval [CI]=1.40-4.28, p=0.0015), and the presence of A2 alleles showed a weak tendency to decrease prostate cancer risk in comparison with the A1/A1 genotype in CYP17 (OR=0.69, 95% CI=0.39-1.23, p=0.21). The stratification of cases according to clinical stage and pathological grade showed that the A2/A2 genotype was significantly associated with localized stage cancer in comparison with metastatic stage cancer (OR=5.18, 95% CI=1.49-17.95, p=0.007). The combination of UGT2B15 and CYP17 genotypes could identify higher risk subjects even in subjects with low-risk UGT2B15 genotypes, i.e., Y/Y+D/Y genotypes (OR=1.97, 95% CI=0.92-4.22, p=0.079).


CONCLUSIONS
Genetic polymorphisms of the genes involved in androgen metabolism and signaling were significantly associated with familial prostate cancer risk. Single nucleotide polymorphisms of low-penetrance genes could be targets to understand genetic susceptibility to familial prostate cancer.
Okugi
Hironobu
H
Department of Urology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511 Gunma, Japan.
Nakazato
Haruki
H
Matsui
Hiroshi
H
Ohtake
Nobuaki
N
Nakata
Seiji
S
Suzuki
Kazuhiro
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012306:Risk; D015398:Signal Transduction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D000728:Androgens; D013254:Steroid 17-alpha-Hydroxylase; D014453:Glucuronosyltransferase; C472000:UDP-glucuronosyltransferase 2B15, human; D017430:Prostate-Specific Antigen