Guo Xiaoqing, Zhang Liwei, Wu Mingli, Wang Na, Liu Yanfeng, Er Limian, Wang Shunping, Gao Yang, Yu Weifang, Xue Hui, Xu Zhibin, Wang Shijie
Department of Endoscopy, The 4th Affiliated Hospital, Hebei Medical University, Hebei, People's Republic of China.
Mol Biol Rep. 2010 Jan;37(1):219-25. doi: 10.1007/s11033-009-9626-z. Epub 2009 Jul 22.
DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29-0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37-1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12-0.84) and males (OR = 0.35, 95% CI = 0.17-0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31-0.96 and OR = 0.48, 95% CI = 0.27-0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.
DNMT3B是一种调节哺乳动物细胞甲基化状态的重要酶。本研究旨在探讨DNMT3B基因G39179T多态性与结直肠腺瘤性息肉及腺癌易感性之间的相关性。这项病例对照研究纳入了146例结直肠腺瘤性息肉患者、170例结直肠癌患者和157例正常对照。采用聚合酶链反应-限制性片段长度多态性分析方法对DNMT3B基因多态性进行分析。结直肠癌家族史显著增加患结直肠腺瘤性息肉和腺癌的风险。腺癌患者中DNMT3B基因多态性（T/T以及G/T + G/G）的基因型频率与对照组相比有显著差异（P值 = 0.01）。与DNMT3B基因T/T基因型相比，G等位基因（G/T + G/G基因型）患结直肠癌的风险较低（OR = 0.50，95%CI = 0.29 - 0.87）；而结直肠腺瘤性息肉患者与对照组之间无显著差异（OR = 0.63，95%CI = 0.37 - 1.09），尽管在该息肉组中可发现下降趋势。在分层分析中，显著关联仅限于年龄<55岁的亚组（OR = 0.31，95%CI = 0.12 - 0.84）和男性亚组（OR = 0.35，95%CI = 0.17 - 0.71）。同时，发现合并G/T + G/G基因型的非饮酒者患结直肠腺瘤性息肉和腺癌的风险较低（分别为OR = 0.54，95%CI = 0.31 - 0.96和OR = 0.48，95%CI = 0.27 - 0.84）。本研究还显示DNMT3B基因G39179T单核苷酸多态性在不同种族中的分布存在明显差异。DNMT3B基因G39179T单核苷酸多态性可能是结肠癌的一个潜在遗传易感因素，尤其是在中国汉族非饮酒的年轻男性中。
