Stanford Janet L, Noonan Elizabeth A, Iwasaki Lori, Kolb Suzanne, Chadwick Robert B, Feng Ziding, Ostrander Elaine A
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle 98109, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Mar;11(3):243-7.
Steroid hormones are important in the etiology and progression of prostate cancer, and expression of genes involved in hormone production may alter susceptibility. One such gene is CYP17, which encodes the cytochrome P450c17a enzyme responsible for the biosynthesis of testosterone. A T to C transition (A2 allele) in the 5' promoter region of the gene is hypothesized to increase the rate of gene transcription, increase androgen production, and thereby increase risk of prostate cancer. To test this hypothesis, germ-line DNA samples from a large population-based study of incident prostate cancer cases (n = 590) and controls (n = 538) of similar age without the disease were genotyped. The frequency of the A2 allele was similar in cases and controls. Compared with men with the A1/A1 genotype, the adjusted odds ratio was 0.81 for the A1/A2 and 0.87 for the A2/A2 genotype. Risk estimates did not vary substantially by age or race. However, stratification by family history of prostate cancer revealed that among white men with an affected first-degree relative, homozygotes for the A2 allele had a significant elevation in risk (odds ratio = 19.2; 95% confidence interval, 2.2-157.4) compared with men who were homozygous for the A1 allele (interaction P = 0.0005). These results suggest that the CYP17 A2/A2 genotype predicts susceptibility to prostate cancer in white men with a family history of the disease. It is also possible that CYP17 interacts with other genes that influence risk of familial prostate cancer.
类固醇激素在前列腺癌的病因学和进展中起着重要作用，参与激素产生的基因表达可能会改变易感性。其中一个这样的基因是CYP17，它编码负责睾酮生物合成的细胞色素P450c17a酶。该基因5'启动子区域的T到C转换（A2等位基因）被认为会增加基因转录速率，增加雄激素产生，从而增加前列腺癌风险。为了验证这一假设，对一项基于人群的大型新发前列腺癌病例（n = 590）和年龄相仿的无病对照（n = 538）的生殖系DNA样本进行了基因分型。A2等位基因在病例组和对照组中的频率相似。与A1/A1基因型的男性相比，A1/A2基因型的校正比值比为0.81，A2/A2基因型为0.87。风险估计在年龄或种族方面没有显著差异。然而，按前列腺癌家族史分层显示，在有一级亲属患癌的白人男性中，A2等位基因纯合子的风险显著升高（比值比 = 19.2；95%置信区间，2.2 - 157.4），相比之下，A1等位基因纯合子男性（交互作用P = 0.0005）。这些结果表明，CYP17 A2/A2基因型可预测有前列腺癌家族史的白人男性对前列腺癌的易感性。CYP17也有可能与其他影响家族性前列腺癌风险的基因相互作用。
