Wani Majid, Afroze Dil, Makhdoomi Muzamil, Hamid Iqra, Wani Bilal, Bhat Gulzar, Wani Rauf, Wani Khursheed
Department of General Surgery, Sher I Kashmir Institute of Medical Sciences, Srinagar, India.
Asian Pac J Cancer Prev. 2012;13(8):4177-81. doi: 10.7314/apjcp.2012.13.8.4177.
Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age (mean ± S.D) 50 ± 11.4 years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001). We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.
癌症是一种多因素疾病，例如，由于基因组错配修复能力的遗传差异导致的遗传易感性变异是胃癌（GC）发生发展的一个重要因素。表观遗传变化，包括错配修复（MMR）基因（如hMLH1）启动子区域5′/CpG岛的异常甲基化，与各种类型GC的发生发展有关。在本研究中，我们评估了hMLH1启动子高甲基化在克什米尔GC患者和对照组中的作用，并评估了其与各种饮食和生活方式因素的相关性。该研究纳入了70例GC患者（56例男性和14例女性；年龄（均值±标准差）50±11.4岁）。通过甲基化特异性聚合酶链反应（MS-PCR）和DNA条带模式实现甲基化和未甲基化的区分。应用卡方检验评估启动子高甲基化导致的风险。我们发现，GC病例中启动子高甲基化的频率显著高于正常样本（GC病例中为72.9%（51/70），正常样本中为20%（14/70），p=0.0001）。我们还观察到，hMLH1基因启动子甲基化与吸烟、食用晒干蔬菜和热咸茶与GC风险之间存在统计学上的显著关联。这项研究表明，hMLH1高甲基化与GC密切相关，并提示表观遗传变化在克什米尔山谷胃癌病因中的作用。
