Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect

Citation
T. Habuchi et al., Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect, CANCER RES, 60(20), 2000, pp. 5710-5713
Citations number
34
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
60
Issue
20
Year of publication
2000
Pages
5710 - 5713
Database
ISI
SICI code
0008-5472(20001015)60:20<5710:IROPCA>2.0.ZU;2-Q
Abstract
The CYP17 gene (CYP17) codes for the cytochrome P450c17 alpha enzyme, which mediates two key steps in the sex steroid synthesis, There is a polymorphi sm (a T-to-C substitution) in the 5'-untranslated region, which may influen ce the transcription level of CYP17 mRNA. There is a continuing controversy as to whether the variant allele is associated with a subset of breast can cer or polycystic ovary syndrome. In prostate cancer research, there are co ntradictory data concerning the CYP17 risk allele. We explored the associat ion between CYP17 polymorphism and a risk of prostate cancer or benign pros tatic hyperplasia (BPH) in a Japanese population. This study included 252 p rostate cancer patients, 202 BFH patients, and 131 male controls, A 451-bp fragment encompassing the polymorphic site was amplified by PCR, treated wi th restriction enzyme MspA1, and electrophoresed on an agarose gel. The Msp A1-undigested allele with the published sequence and the MspA1-digested var iant allele were designated as Al and AZ, respectively, There was a signifi cant difference (P < 0.05) in the genotypes between prostate cancer patient s and male controls, and between BPH patients and male controls, Men with t he A1/A1 CYP17 genotype had an increased risk of prostate cancer [odds rati o (OR), 2.57; 95% confidence interval (CI) = 1.39-4.78] and BPH (OR, 2.44; 95% CI = 1.26-4.72) compared with those with the A2/A2 genotype, Men with t he A1/A2 genotype had an intermediate increased risk of prostate cancer (OR , 1.45; 95% CI = 0.84-2.54) and BPH (OR, 1.60; 95% CI = 0.89-2.87) compared with those with the A2/A2 genotype. The trend of an increasing risk of pro state cancer and BPH with an increasing number of the Al allele was statist ically significant (prostate cancer versus male control, P = 0.003; OR, 1.5 7; 95% CI = 1.16-2.12; BPH versus male control, P = 0.008; OR, 1.55; 95% CI = 1.12-2.13), There was no significant association between the CYP17 genot ype and the tumor status (grade and stage) of prostate cancer. Our results suggest that the Al allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and BPH, with a gene dosage effect. Howev er, the CYP17 genotype does not seem to influence the disease status in pro state cancer.