You Wei-cheng, Hong Jun-Yan, Zhang Lian, Pan Kai-feng, Pee David, Li Ji-you, Ma Jun-ling, Rothman Nathaniel, Caporaso Neil, Fraumeni Joseph F, Xu Guang-wei, Gail Mitchell H
Peking University School of Oncology, Beijing Cancer Hospital and Beijing Institute for Cancer Research, #52 Fu-Cheng Road, Haidian District, Beijing 100036, People's Republic of China.
Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):451-8. doi: 10.1158/1055-9965.EPI-04-0311.
There have been few studies of the associations of genetic polymorphisms with precancerous gastric lesions. We conducted a cross-sectional study to compare the prevalences of several genetic polymorphisms in 302 subjects with mild chronic atrophic gastritis with prevalences in 606 subjects with deep intestinal metaplasia or dysplasia. This stratified random sample of 908 subjects was selected and analyzed for genetic polymorphisms from 2,628 individuals who had gastric biopsies with histopathology in 1989 in Linqu County, Shandong Province, China. In subjects with mild chronic atrophic gastritis, the frequencies of the variant (less common) alleles of CYP2E1 RsaI, CYP2E1 DraI, GSTP1, ALDH2, and ODC were, respectively, 0.156, 0.201, 0.189, 0.190, and 0.428. The frequencies of the null genotypes of GSTM1 and GSTT1 in the mild chronic atrophic gastritis group were 0.509 and 0.565, respectively. Comparing mild chronic atrophic gastritis with deep intestinal metaplasia or any degree of dysplasia, we found no statistically significant associations with any genotype from these loci for dominant, additive, or recessive inheritance models. There was no statistically significant evidence of multiplicative interactions between any pair of genotypes based on CYP2E1 RsaI, CYP2E1 DraI, GSTP1, GSTM1, or GSTT1; nor between Helicobacter pylori status and any of these five loci; nor between smoking status and GSTP1, GSTM1, or GSTT1; nor between alcohol consumption and ALDH2. Statistically significant interactions were noted between salt consumption and GSTP1 and between sour pancake consumption and CYP2E1 RsaI. There was, moreover, a statistically significant interaction (odds ratio, 1.78; 95% confidence interval, 1.03-3.08) between CYP2E1 DraI and smoking at least one cigarette per day. A positive but not statistically significant interaction was also seen between CYP2E1 RsaI and smoking status. These polymorphisms do not seem to govern progression from mild chronic atrophic gastritis to advanced precancerous gastric lesions, but the effects of smoking may be accentuated in individuals carrying variants of CYP2E1.
关于基因多态性与胃癌前病变之间关联的研究较少。我们开展了一项横断面研究，比较了302例轻度慢性萎缩性胃炎患者与606例重度肠化生或异型增生患者中几种基因多态性的患病率。该分层随机样本中的908例受试者是从1989年在中国山东省临朐县进行胃活检并伴有组织病理学检查的2628例个体中选取并分析其基因多态性的。在轻度慢性萎缩性胃炎患者中，CYP2E1 RsaI、CYP2E1 DraI、GSTP1、ALDH2和ODC变异（较罕见）等位基因的频率分别为0.156、0.201、0.189、0.190和0.428。轻度慢性萎缩性胃炎组中GSTM1和GSTT1无效基因型的频率分别为0.509和0.565。将轻度慢性萎缩性胃炎与重度肠化生或任何程度的异型增生进行比较，我们发现对于显性、加性或隐性遗传模型，这些基因座的任何基因型之间均无统计学上的显著关联。基于CYP2E1 RsaI、CYP2E1 DraI、GSTP1、GSTM1或GSTT1的任何一对基因型之间，幽门螺杆菌感染状态与这五个基因座中的任何一个之间，吸烟状态与GSTP1、GSTM1或GSTT1之间，饮酒与ALDH2之间，均无统计学上显著的相互作用证据。在盐摄入量与GSTP1之间以及酸煎饼摄入量与CYP2E1 RsaI之间观察到有统计学意义的相互作用。此外，CYP2E1 DraI与每天至少吸一支烟之间存在统计学上显著的相互作用（优势比，1.78；95%置信区间，1.03 - 3.08）。CYP2E1 RsaI与吸烟状态之间也观察到正向但无统计学意义的相互作用。这些多态性似乎并不决定从轻度慢性萎缩性胃炎进展为晚期胃癌前病变，但吸烟对携带CYP2E1变异的个体的影响可能会增强。
