Al-Moundhri Mansour S, Alkindy Mohamed, Al-Nabhani Maryam, Al-Bahrani Bassim, Burney Ikram A, Al-Habsi Hamdan, Ganguly Shyam S, Tanira Musbah
Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
J Clin Gastroenterol. 2009 Feb;43(2):152-6. doi: 10.1097/MCG.0b013e31815853fa.
Host genetics have been implicated in gastric cancer carcinogenesis. Polymorphisms of glutathione S-transferase (GST) M1 and G1 and of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) were shown to increase gastric cancer predisposition in several studies. To our knowledge, this is the first report on the combined analysis of polymorphisms GSTM1/G1 and IL-1B/IL-1RN genes in gastric adenocarcinoma.
Genomic DNA was extracted from peripheral blood of 107 control subjects and 107 gastric cancer patients. Analysis for the GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction. The DNA samples were analyzed using the TaqMan allelic discrimination test for the polymorphism of IL-1B at positions-31. The variable number of tandem repeats of IL-1RN was genotyped using polymerase chain reaction followed by agarose gel electrophoresis.
There were no statistically significant associations between the GSTM1/G1 or IL-1B-31 genes and gastric cancer risk. There was a statistical association between the presence of the IL-1RN2 allele and gastric cancer (odds ratio 2.2, 95% confidence interval=1.2-3.7, P=0.01). Combined analysis showed that a combination of the null GSTM1 genotype and carriers of IL-1RN2 was associated with a statistically significant correlation with gastric cancer (odds ratio=3.6, 95% confidence interval=1.4-9.4, P=0.008).
The current study suggests that the individual variation in both the cellular inflammatory modulator IL-1RN and the antioxidative property of GSTM1 may predispose individuals to an increased risk of gastric cancer.
宿主遗传学与胃癌致癌作用有关。多项研究表明，谷胱甘肽S-转移酶（GST）M1和G1以及白细胞介素-1β（IL-1β）和白细胞介素-1受体拮抗剂（IL-1RN）的多态性会增加胃癌易感性。据我们所知，这是关于胃腺癌中GSTM1/G1和IL-1β/IL-1RN基因多态性联合分析的首篇报道。
从107名对照受试者和107名胃癌患者的外周血中提取基因组DNA。通过多重聚合酶链反应对GSTM1和GSTT1基因多态性进行分析。使用TaqMan等位基因鉴别试验对DNA样本中IL-1β基因-31位点的多态性进行分析。采用聚合酶链反应随后进行琼脂糖凝胶电泳对IL-1RN的可变串联重复序列进行基因分型。
GSTM1/G1或IL-1β -31基因与胃癌风险之间无统计学显著关联。IL-1RN2等位基因的存在与胃癌之间存在统计学关联（优势比2.2，95%置信区间=1.2 - 3.7，P = 0.01）。联合分析显示，GSTM1基因无效基因型与IL-1RN2携带者的组合与胃癌存在统计学显著相关性（优势比=3.6，95%置信区间=1.4 - 9.4，P = 0.008）。
当前研究表明，细胞炎症调节因子IL-1RN和GSTM1抗氧化特性的个体差异可能使个体患胃癌的风险增加。
