Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites
Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites
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DOI：
10.1002/pros.10236
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发表时间：
2003-05-15
期刊：
影响因子：
2.8
通讯作者：
Tangrea, J
中科院分区：
文献类型：
--
作者：
Woodson, K;Hayes, R;Tangrea, J
背景。在美国，美国黑人前列腺癌的发病率和死亡率大约是白人的两倍，这表明前列腺肿瘤的发病率和侵袭性存在种族差异。造成这些种族差异的原因尚不清楚。表观遗传事件，如启动子区基因高甲基化可能受到环境暴露的影响，并与前列腺癌的发生有关（通过肿瘤抑制基因和其他调控基因的沉默）。使用实时甲基化敏感PCR，我们评估了黑人（n = 47）和白人（n = 64）档案肿瘤组织中GSTP1、CD44和E-cadherin（三个被认为在前列腺癌进展中很重要的基因）DNA超甲基化的差异。我们发现GSTP1高甲基化的总体患病率很高（84%），但没有种族差异（黑人男性与白人男性分别为89%和83%），肿瘤分期或分级。虽然CD44高甲基化总体上不太普遍（在32%的肿瘤中发现），但我们观察到黑人男性的频率高1.7倍（43% vs. 25%，黑人vs.白人，P = 0.05），并且与肿瘤级别相关（CD44高甲基化分别在10%、42%和52%的良好、中度和低分化肿瘤中发生，P = 0.003），但与疾病分期无关。e -钙粘蛋白基因在任何肿瘤中均未出现高甲基化。总之，在检测的三个基因中，只有CD44高甲基化与种族不同，与肿瘤分级相关，与种族无关。这些初步发现表明，基因启动子超甲基化的差异可能是前列腺癌发病机制中种族差异的潜在基础，应该在更大规模的研究中进行探索。(C) 2003 Wiley-Liss, Inc。
BACKGROUND. In the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter-region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes).METHODS. Using real-time methylation-sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E-cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64).RESULTS. We found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7-fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E-cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race.CONCLUSIONS. These preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies. (C) 2003 Wiley-Liss, Inc.