Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Anticancer Res. 2011 Apr;31(4):1459-65.
Genetic factors related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to Helicobacter pylori (H. pylori)-related gastric carcinogenesis. The association between XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms with gastric intestinal metaplasia, severity of histological gastritis, and peptic ulcer diseases were evaluated in a Japanese population.
XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val and GSTT1, GSTM1 null polymorphisms were genotyped in 280 cancer-free individuals, including 52 gastric and 31 duodenal ulcer patients.
Among the five polymorphisms, a significant association between the GSTT1 and GSTM1 null genotypes and increased risk of intestinal metaplasia was found (GSTT1 null: OR=2.42, 95% CI=1.28-4.60, p=0.007, GSTM1 null: OR=2.18, 95% CI=1.15-4.13, p=0.019). When the severity of gastric atrophy was classified into the following three groups: non-atrophy (NA) (atrophy score=0 and metaplasia score=0); severe atrophy (SA) (atrophy score≥2 or metaplasia score≥2) and mild atrophy (MA) (all others), both the GSTT1 and GSTM1 null genotypes held significantly higher risk for developing more severe gastric atrophy (GSTT1 null, SA vs. others: OR=1.95, 95% CI=1.07-3.52, p=0.028, GSTM1 null, NA vs. others: OR=2.57, 95% CI=1.16-5.67, p=0.019, SA vs. others: OR=1.90, 95% CI=1.06-3.42, p=0.032). A significant association was also found between GSTM1 null genotype and increased risk of ulcer diseases (all ulcers: OR=2.42, 95% CI=1.37-4.26, p=0.002, gastric ulcer: OR=2.18, 95% CI=1.11-4.29, p=0.025, duodenal ulcer: OR=2.62, 95% CI=1.15-6.00, p=0.023).
Both the GSTT1 and GSTM1 null genotypes are associated with gastric pre-malignant conditions.
与 DNA 修复或异生物质途径相关的遗传因素可能赋予了对幽门螺杆菌（H. pylori）相关胃致癌作用的不同程度的易感性。在日本人群中，评估了 XRCC1 Arg399Gln 和 Arg194Trp、GSTP1 Ile104Val 和 GSTT1、GSTM1 缺失多态性与胃肠上皮化生、组织学胃炎严重程度和消化性溃疡病之间的关系。
在 280 例无癌症个体中，包括 52 例胃癌和 31 例十二指肠溃疡患者，对 XRCC1 Arg399Gln 和 Arg194Trp、GSTP1 Ile104Val 和 GSTT1、GSTM1 缺失多态性进行了基因分型。
在这五个多态性中，发现 GSTT1 和 GSTM1 缺失基因型与肠上皮化生的风险增加之间存在显著关联（GSTT1 缺失：OR=2.42，95%CI=1.28-4.60，p=0.007，GSTM1 缺失：OR=2.18，95%CI=1.15-4.13，p=0.019）。当胃萎缩的严重程度分为以下三组时：非萎缩（NA）（萎缩评分=0 和化生评分=0）；严重萎缩（SA）（萎缩评分≥2 或化生评分≥2）和轻度萎缩（MA）（所有其他），GSTT1 和 GSTM1 缺失基因型均显著增加了发展为更严重胃萎缩的风险（GSTT1 缺失，SA 与其他：OR=1.95，95%CI=1.07-3.52，p=0.028，GSTM1 缺失，NA 与其他：OR=2.57，95%CI=1.16-5.67，p=0.019，SA 与其他：OR=1.90，95%CI=1.06-3.42，p=0.032）。还发现 GSTM1 缺失基因型与溃疡病的风险增加之间存在显著关联（所有溃疡：OR=2.42，95%CI=1.37-4.26，p=0.002，胃溃疡：OR=2.18，95%CI=1.11-4.29，p=0.025，十二指肠溃疡：OR=2.62，95%CI=1.15-6.00，p=0.023）。
GSTT1 和 GSTM1 缺失基因型均与胃前恶性病变相关。
