Mononen N, Ikonen T, Syrjäkoski K, Matikainen M, Schleutker J, Tammela T L, Koivisto P A, Kallioniemi O P
Laboratory of Cancer Genetics, Dept. of Clinical Chemistry, Institution of Medical Technology, University of Tampere and Tampere University Hospital, P.O. Box 2000, Tampere, FIN-33521, Finland.
Br J Cancer. 2001 May 18;84(10):1344-7. doi: 10.1054/bjoc.2001.1789.
Prostatic steroid 5-alpha-reductase gene (SRD5A2) encodes a critical enzyme involved in the conversion of testosterone to dihydrotestosterone. A germline mis-sense substitution (A49T) leads to a variant SRD5A2 protein, which has a 5-fold higher in vitro V(max)than the wild-type protein (Ross et al, 1998; Makridakis et al, 1999). The A49T variant was recently associated with 2.5 to 3.28-fold increased risk of prostate cancer (PC) in African-American and Hispanic men (Makridakis et al, 1999). Also, Jaffe et al (2000) reported an association between A49T and more aggressive disease among Caucasian patients. Here, we report that the prevalence of the A49T variant in 449 Finnish PC patients was 6.0%, not significantly different from 6.3% observed in 223 patients with benign prostatic hyperplasia or 5.8% in 588 population-based controls (odds ratio for PC 1.04, 95% C.I. 0.62-1.76, P = 0.89). There was no association between A49T and the family history of the patients nor with tumour stage or grade. Our results argue against a prominent role of the A49T variant as a genetic risk factor for prostate cancer development and progression in the Finnish population.
前列腺类固醇5-α还原酶基因(SRD5A2)编码一种关键酶,参与睾酮向双氢睾酮的转化。一种生殖系错义替代(A49T)导致一种变异的SRD5A2蛋白,其体外V(max)比野生型蛋白高5倍(罗斯等人,1998年;马克里达基斯等人,1999年)。最近发现,在非裔美国人和西班牙裔男性中,A49T变异与前列腺癌(PC)风险增加2.5至3.28倍有关(马克里达基斯等人,1999年)。此外,贾菲等人(2000年)报告了在白种人患者中A49T与更具侵袭性疾病之间的关联。在此,我们报告449名芬兰PC患者中A49T变异的患病率为6.0%,与223名良性前列腺增生患者中观察到的6.3%或588名基于人群的对照者中的5.8%无显著差异(PC的优势比为1.04,95%置信区间0.62 - 1.76,P = 0.89)。A49T与患者的家族史、肿瘤分期或分级均无关联。我们的结果表明,在芬兰人群中,A49T变异作为前列腺癌发生和进展的遗传风险因素不起主要作用。