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西非男性前列腺癌中的TMPRSS2:ERG基因融合及种族差异的荟萃分析

TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences.

作者信息

Zhou Cindy Ke, Young Denise, Yeboah Edward D, Coburn Sally B, Tettey Yao, Biritwum Richard B, Adjei Andrew A, Tay Evelyn, Niwa Shelley, Truelove Ann, Welsh Judith, Mensah James E, Hoover Robert N, Sesterhenn Isabell A, Hsing Ann W, Srivastava Shiv, Cook Michael B

机构信息

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of Health Sciences, Rockville, Maryland.

出版信息

Am J Epidemiol. 2017 Dec 15;186(12):1352-1361. doi: 10.1093/aje/kwx235.

Abstract

The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004-2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.

摘要

跨膜蛋白酶丝氨酸2基因(TMPRSS2)与成红细胞转化特异性相关基因(ERG)的融合,即TMPRSS2:ERG,在前列腺癌中的发生率因种族而异。然而,这种体细胞畸变及其与预后因素的关联在西非人群中尚未得到研究,在种族差异的背景下也未得到系统综述。我们采用免疫组织化学方法,在加纳前列腺研究(2004 - 2006年)的262份前列腺癌活检样本中,评估由ERG基因编码的癌蛋白,作为ERG融合基因的既定替代指标。采用稳健方差估计的泊松回归分析得出ERG表达与患者特征相关的患病率比及95%置信区间。我们发现,262例前列腺癌中有47例(18%)ERG呈阳性,ERG染色阴性与更高的 Gleason评分相关。我们进一步对TMPRSS2:ERG融合与种族、Gleason评分和肿瘤分期的关系进行了系统综述和荟萃分析,将加纳的结果与另外40项研究的结果相结合。荟萃分析显示,前列腺癌中TMPRSS2:ERG融合的发生率在欧洲裔男性中最高(49%),其次是亚裔男性(27%),然后是非洲裔男性(25%)。非洲裔男性中TMPRSS2:ERG融合的发生率较低,这意味着其他基因组机制可能解释了此类人群中前列腺癌负担过高的现象。

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