Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China.
Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China.
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发表时间：
2003-11
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通讯作者：
R. Stolzenberg-Solomon;Y. Qiao;C. Abnet;D. Ratnasinghe;S. Dawsey;Z. Dong;P. Taylor;S. Mark
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作者：
R. Stolzenberg-Solomon;Y. Qiao;C. Abnet;D. Ratnasinghe;S. Dawsey;Z. Dong;P. Taylor;S. Mark
林县是中国中北部的一个农村县，是世界上食管鳞状细胞癌（ESCC）和贲门腺癌（GCA）发病率最高的地区之一。居民记录了慢性营养不良，包括叶酸和维生素B（12）缺乏。使用我们自1985年以来一直在林县研究的队列，我们检查了ESCC和GCA癌症事件之间的关系，以及编码需要叶酸和B（12）作为辅助因子的酶的两个基因中的三个多态性：甲硫氨酸合成酶还原酶（MTRR）A66 G和亚甲基四氢叶酸还原酶（MTHFR）C677 T和A1298 C。我们对4005名在1991年存活且无癌症的个体进行了一项病例队列研究，这些个体的血液样本足以提取DNA。对1996年5月发生的所有219例癌症（129例ESCC和90例GCA）和398例对照组进行了多态性检测。使用考克斯比例风险模型估计相对风险（RR）和95%置信区间（CI）。MTHFR 677 TT基因型个体的ESCC/GCA合并风险显著高于CC或CT基因型个体（RR，1.45; 95%CI，1.02-2.05）。仅有3例ESCC患者存在MTHFR 1298 CC（P = 0.03）。与MTRR 66 AA基因型相比，AG或GG基因型的受试者发生ESCC的风险显著增高（RR，1.59; 95% CI，1.04-2.42）。未观察到GCA相关性。我们的研究结果表明，MTHFR C677 T和MTRR A66 G多态性影响ESCC和GCA在这一人群中的风险。
Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B(12) deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B(12) as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04-2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population.