Ratnasinghe Luke D, Abnet Christian, Qiao You-Lin, Modali Rama, Stolzenberg-Solomon Rachael, Dong Zhi-Wei, Dawsey Sanford M, Mark Steven D, Taylor Philip R
Center for Structural Genomics, NCTR, Food and Drug Administration, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas, AR 72079-9502, USA.
Cancer Lett. 2004 Dec 28;216(2):157-64. doi: 10.1016/j.canlet.2004.03.012.
Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world. In a nested case-cohort study that originated from two cancer prevention trials in Linxian, we examined the relationship between these cancers and two polymorphisms in the DNA repair gene XRCC1.
We conducted a case-cohort study among individuals in the cohort who were alive and cancer free in 1991, and had blood samples for DNA extraction. Real time Taqman analyses were conducted to genotype incident cancer cases (n = 221, 131 esophageal and 90 gastric cardia cancer cases) that developed through May 1996, and on an age- and sex-matched reference cohort (n = 454). We used Cox proportional hazard models to estimate relative risks (RR) and 95% confidence intervals (95% CI).
We observed no association between the variant genotype in XRCC1 Arg194Trp (codon 194 arganine to tryptophan substitution) and esophageal or gastric cardia cancer. However, carrying at least one copy of the variant allele in XRCC1 Arg399Gln (codon 399 arganine to glutamine substitution) was associated with reduced risk of gastric cardia cancer (RR: 0.60, 95% CI: 0.37-0.97) and the combined category esophageal/gastric cancer (RR: 0.67, 95% CI: 0.48-0.95). In combined polymorphisms analyses, we observed a significant reduction in risk of combined esophageal/gastric cancer among individuals that had both the XRCC1 Arg194Trp and Arg399Gln variant genotyopes (RR: 0.47, 95% CI: 0.26-0.84).
Our results suggest that the XRCC1 Arg399Gln variant genotype is associated with reduced risk of upper GI cancer and that individuals with both XRCC1 variant genotypes are also at significantly reduced risk of upper GI cancer in this high-risk Chinese population.
中国中北部的一个乡村县林县，是世界上食管鳞状细胞癌和贲门腺癌发病率最高的地区之一。在一项源于林县两项癌症预防试验的巢式病例对照研究中，我们研究了这些癌症与DNA修复基因XRCC1中的两种多态性之间的关系。
我们对1991年队列中存活且无癌症的个体进行了病例对照研究，这些个体有用于DNA提取的血样。对截至1996年5月发生的新发癌症病例（n = 221，其中131例为食管癌病例，90例为贲门癌病例）以及年龄和性别匹配的对照队列（n = 454）进行实时Taqman分析以进行基因分型。我们使用Cox比例风险模型来估计相对风险（RR）和95%置信区间（95%CI）。
我们未观察到XRCC1基因Arg194Trp（密码子194处精氨酸替换为色氨酸）的变异基因型与食管癌或贲门癌之间存在关联。然而，携带XRCC1基因Arg399Gln（密码子399处精氨酸替换为谷氨酰胺）至少一个拷贝的变异等位基因与贲门癌风险降低相关（RR：0.60，95%CI：0.37 - 0.97）以及食管/胃癌联合类型（RR：0.67，95%CI：0.48 - 0.95）。在联合多态性分析中，我们观察到同时具有XRCC1基因Arg194Trp和Arg399Gln变异基因型的个体中，食管/胃癌联合风险显著降低（RR：0.47，95%CI：0.26 - 0.84）。
我们的结果表明，XRCC1基因Arg399Gln变异基因型与上消化道癌症风险降低相关，并且在这个高危中国人群中，同时具有两种XRCC1变异基因型的个体上消化道癌症风险也显著降低。
