Sugimoto Mitsushige, Furuta Takahisa, Shirai Naohito, Ikuma Mutsuhiro, Sugimura Haruhiko, Hishida Akira
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan.
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1929-34. doi: 10.1158/1055-9965.EPI-06-0339.
The renin-angiotensin system plays an important role in homeostasis. Angiotensin II, which is generated by chymase and angiotensin I-converting enzyme (ACE), controls blood pressure as well as angiogenesis and cell proliferation. The aim of this study was to clarify the association of the chymase gene (CMA/B) and ACE polymorphisms with susceptibility to gastric cancer and peptic ulcer.
We assessed CMA/B A/G and ACE insertion/deletion (I/D) polymorphisms in H. pylori-positive gastric cancers (n = 119), gastric ulcers (n = 127), and duodenal ulcers (n = 105), and controls (n = 294) consisting of H. pylori-positive gastritis alone (n = 162) and H. pylori-negative subjects (n = 132) by PCR methods.
In CMA/B polymorphism, the age- and sex-adjusted odds ratios (OR) of A/A and A/G genotypes relative to the G/G genotype for gastric cancer risk were 7.115 (95% confidence interval, 1.818-27.845) and 1.956 (95% confidence interval, 1.137-3.366), respectively. There was an increased risk for gastric ulcer in the A/A genotype (OR, 3.450; 1.086-10.960). However, there was no association between ACE polymorphism and susceptibility to gastric cancer and peptic ulcer. In allele combination analysis of CMA/B and ACE polymorphisms, the A/I allele combinations (CMA/B G/A or A/A and ACE I/I genotype) significantly increased the risk of gastric cancer development (OR, 4.749, 2.050-11.001) compared with the G/I allele combinations (CMA/B G/G and ACE I/I genotype).
The CMA/B polymorphism was associated with an increased risk for gastric cancer and gastric ulcer development. The genotyping test of the renin-angiotensin system could be useful for the screening of individuals with higher risks of gastric cancer and gastric ulcer.
肾素 - 血管紧张素系统在体内稳态中起重要作用。由糜酶和血管紧张素I转换酶（ACE）产生的血管紧张素II控制血压以及血管生成和细胞增殖。本研究的目的是阐明糜酶基因（CMA/B）和ACE基因多态性与胃癌和消化性溃疡易感性之间的关联。
我们通过PCR方法评估了幽门螺杆菌阳性的胃癌患者（n = 119）、胃溃疡患者（n = 127）、十二指肠溃疡患者（n = 105）以及对照组（n = 294，包括单独的幽门螺杆菌阳性胃炎患者（n = 162）和幽门螺杆菌阴性受试者（n = 132））的CMA/B A/G和ACE插入/缺失（I/D）多态性。
在CMA/B多态性中，相对于G/G基因型，胃癌风险的A/A和A/G基因型经年龄和性别调整后的优势比（OR）分别为7.115（95%置信区间，1.818 - 27.845）和1.956（95%置信区间，1.137 - 3.366）。A/A基因型的胃溃疡风险增加（OR，3.450；1.086 - 10.960）。然而，ACE多态性与胃癌和消化性溃疡易感性之间无关联。在CMA/B和ACE多态性的等位基因组合分析中，与G/I等位基因组合（CMA/B G/G和ACE I/I基因型）相比，A/I等位基因组合（CMA/B G/A或A/A和ACE I/I基因型）显著增加了胃癌发生风险（OR，4.749，2.050 - 11.001）。
CMA/B多态性与胃癌和胃溃疡发生风险增加相关。肾素 - 血管紧张素系统的基因分型检测可能有助于筛查胃癌和胃溃疡高风险个体。
