Hanaoka T, Sugimura H, Nagura K, Ihara M, Li X J, Hamada G S, Nishimoto I, Kowalski L P, Yokota J, Tsugane S
Epidemiology and Biostatistics Division, National Cancer Center Research Institute East, 6-5-1 Kashinoha, Kashiwa-shi, 277-8577, Chiba, Japan.
Cancer Lett. 2001 Sep 10;170(1):53-61. doi: 10.1016/s0304-3835(01)00565-1.
Polymorphism of hOGG1 may be capable of serving as a genetic marker for individual susceptibility to various cancers because of its role in the repair of oxyradical DNA damage. We examined the distribution of the hOGG1 Ser326Cys polymorphism and its presumed correlation with gastric cancer risk in two case-control studies of different ethnic groups in São Paulo, Brazil. Potentially eligible Japanese (JB) and non-Japanese Brazilian (NJB) case subjects were defined as patients with newly diagnosed malignant neoplasms of the stomach in 13 hospitals in São Paulo. Ninety-six JBs and 236 NJBs were adopted as subjects. Two controls were matched for each JB case, and one control for each NJB case. The subjects were interviewed using a questionnaire and their blood samples were collected. A significant difference in the distribution of this polymorphism between the two ethnic groups was observed (chi(2)=58.3, P<0.01). The mutant type (Ser/Cys or Cys/Cys) was predominant (approximately 65%) in the JBs, but was only present in approximately 40% of the NJBs. Logistic regression analysis showed no significant increased risk for either the Ser/Cys or Cys/Cys type in either group. The odds ratios of the Cys allele for gastric cancer were 1.01 (95% confidence interval (CI): 0.52-1.93) in the JBs and 0.85 (95% CI: 0.57-1.26) in the NJBs. In the NJBs, a significant increased risk of smoking was shown only in the Ser/Ser type, and no increased risk was shown in the genotypes with the Cys allele. However, no statistically significant interactions were observed with smoking or other possible confounding factors. No statistically significant difference in the distribution of the polymorphism was observed between the intestinal type and diffuse type of gastric cancer in either the JBs or the NJBs. The ethnic difference in hOGG1 Ser326Cys polymorphism was much greater than the case-control difference, and this polymorphism is unlikely to be associated with gastric cancer.
hOGG1基因多态性可能因其在修复氧自由基DNA损伤中的作用，而能够作为个体对各种癌症易感性的遗传标记。我们在巴西圣保罗针对不同种族群体开展的两项病例对照研究中，检测了hOGG1 Ser326Cys多态性的分布及其与胃癌风险的假定相关性。潜在符合条件的日本裔巴西人（JB）和非日本裔巴西人（NJB）病例被定义为圣保罗13家医院中，新诊断为胃恶性肿瘤的患者。96名JB和236名NJB被纳入研究对象。每个JB病例匹配两名对照，每个NJB病例匹配一名对照。使用问卷对研究对象进行访谈，并采集他们的血样。观察到两个种族群体之间该多态性的分布存在显著差异（卡方值=58.3，P<0.01）。突变型（Ser/Cys或Cys/Cys）在JB中占主导地位（约65%），但在NJB中仅约40%存在。逻辑回归分析显示，两组中Ser/Cys或Cys/Cys型的风险均未显著增加。JB中Cys等位基因患胃癌的比值比为1.01（95%置信区间（CI）：0.52 - 1.93），NJB中为0.85（95%CI：0.57 - 1.26）。在NJB中，仅Ser/Ser型显示吸烟风险显著增加，而含Cys等位基因的基因型未显示风险增加。然而，未观察到与吸烟或其他可能混杂因素的统计学显著相互作用。在JB或NJB中，肠型和弥漫型胃癌之间在多态性分布上未观察到统计学显著差异。hOGG1 Ser326Cys多态性的种族差异远大于病例对照差异，且这种多态性不太可能与胃癌相关。
