DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study
DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study
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DOI：
10.1093/ije/dyn145
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发表时间：
2008-12-01
影响因子：
7.7
通讯作者：
Gonzalez, Carlos A.
中科院分区：
文献类型：
--
作者：
Capella, Gabriel;Pera, Guillem;Gonzalez, Carlos A.
DNA修复基因的遗传变异对胃癌（GC）风险的影响仍然是未知的。本研究的目的是探讨DNA修复基因多态性对胃癌风险和严重慢性萎缩性胃炎（SCAG）的相对贡献。方法在EPIC队列中进行巢式病例对照研究，包括246例胃腺癌患者和1175名匹配的对照组。还比较了胃蛋白酶原A （PGA）水平低的SCAG对照组（n 91）和无SCAG对照组（n 1061）。分析了DNA修复基因（MSH2、MLH1、XRCC1、OGG1和ERCC2）和TP53基因的12个多态性。检测幽门螺杆菌抗体。结果没有观察到这些多态性与胃癌风险的关联。然而，ERCC2 K751Q多态性与非心脏肿瘤风险增加相关[优势比（OR） 1.78；[95可信区间（CI） 1.023.12]，即ERCC2 K751Q和D312N多态性与弥漫型相关。ERCC2 D312N （OR 2.0; 95 CI 1.093.65）和K751Q等位基因（OR 1.82; 95 CI 1.013.30）和XRCC1 R399Q （OR 1.69; 95 CI 1.022.79）等位基因与SCAG风险增加相关。结论我们的研究支持ERCC2在非心源性GC中的作用，但在心源性癌中没有作用。在PGA水平较低的受试者中观察到一致的结果。XRCC1等位基因也与SCAG相关。这是第一项前瞻性研究，表明DNA修复的个体差异可能与胃癌发生有关，这一发现将需要在更大规模的独立研究中进一步证实。
Background The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG).Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured.Results No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) 1.78; 95 confidence interval (CI) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) allele were associated with an increased risk for SCAG.Conclusion Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.