Increased Risk of Prostate Cancer and Benign Prostatic Hyperplasia Associated with a CYP17 Gene Polymorphism with a Gene Dosage Effect
2000
The CYP17 gene ( CYP17 ) codes for
the cytochrome P450c17α enzyme, which mediates two key steps in the
sex steroid synthesis. There is a polymorphism (a T-to-C substitution)
in the 5′-untranslated region, which may influence the transcription
level of CYP17 mRNA. There is a continuing controversy
as to whether the variant allele is associated with a subset of breast
cancer or polycystic ovary syndrome. In prostate cancer research, there
are contradictory data concerning the CYP17 risk allele.
We explored the association between CYP17
polymorphism and a risk of prostate cancer or benign prostatic
hyperplasia (BPH) in a Japanese population. This study included 252
prostate cancer patients, 202 BPH patients, and 131 male controls. A
451-bp fragment encompassing the polymorphic site was amplified by PCR,
treated with restriction enzyme Msp A1, and
electrophoresed on an agarose gel. The Msp A1-undigested
allele with the published sequence and the
Msp A1-digested variant allele were designated as A1 and
A2, respectively. There was a significant difference
( P < 0.05) in the genotypes between
prostate cancer patients and male controls, and between BPH patients
and male controls. Men with the A1/A1 CYP17 genotype had
an increased risk of prostate cancer [odds ratio (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 the 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 prostate cancer and BPH with an increasing number of
the A1 allele was statistically significant (prostate cancer
versus male control, P = 0.003; OR, 1.57; 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 genotype and
the tumor status (grade and stage) of prostate cancer. Our results
suggest that the A1 allele of the CYP17 polymorphism is
associated with an increased risk of prostate cancer and BPH,
with a gene dosage effect. However, the CYP17 genotype
does not seem to influence the disease status in prostate cancer.
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