Genetic variants in XRCC2: new insights into colorectal cancer tumorigenesis.
Genetic variants in XRCC2: new insights into colorectal cancer tumorigenesis.
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XRCC2中的遗传变异：对结直肠癌肿瘤发生的新见解。
DOI：
10.1158/1055-9965.epi-09-0187
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发表时间：
2009-09
期刊：
影响因子：
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通讯作者：
Colorectal Cancer Study Group
中科院分区：
文献类型：
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作者：
Curtin K;Lin WY;George R;Katory M;Shorto J;Cannon-Albright LA;Smith G;Bishop DT;Cox A;Camp NJ;Colorectal Cancer Study Group
双链DNA修复基因XRCC 2的多态性可能在结直肠癌（CRC）的病因学中发挥重要作用，特别是在疾病亚型中。XRCC 2变异体和CRC的关联性通过肿瘤部位和肿瘤不稳定状态进行了研究，包括三个英国研究中心。病例对照研究（谢菲尔德、利兹、邓迪）和美国高风险犹他州家系病例的病例对照研究（总计：1，252例病例，1，422例对照）。研究的14种变体是从HapMap/NIEHS数据中选择的标记SNP，并补充了从125例选择代表多个CRC组（家族性、转移性疾病和肿瘤亚位点）的测序中鉴定的SNP。使用Genie软件的Monte Carlo显著性检验提供了对包括基于家庭的数据在内的总资源的有效Meta分析。与CRC和其他癌症部位的报告相似，rs3218536 R188 H等位基因与风险增加无关。然而，我们观察到一种新的，高度显著的常见SNP rs3218499 G>C与直肠肿瘤风险增加的相关性（OR 2.1，95%CI 1.3-3.3; pchisq. =0.0006）与对照组相比，女性直肠癌病例的风险最大（OR 3.1，95%CI 1.6-6.1; pchisq. =0.0006）。这种差异与近端和远端结肠癌的差异显著不同（pchisq. =0.02）。我们的研究支持XRCC 2在CRC肿瘤发生中的作用，赋予直肠肿瘤的易感性。
Polymorphisms in double-strand DNA repair gene XRCC2 may play an important role in colorectal cancer (CRC) etiology, specifically in disease subtypes. Associations of XRCC2 variants and CRC were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases, 1,422 controls). The 14 variants studied were tagging-SNPs selected from HapMap/NIEHS data, supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple CRC groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta analyses of the total resource that includes family-based data. Similar to reports of CRC and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G>C, with increased risk of rectal tumors (OR 2.1, 95%CI 1.3-3.3; pchisq. =0.0006) versus controls, with the largest risk found for female rectal cases (OR 3.1, 95%CI 1.6-6.1; pchisq. =0.0006). This difference was significantly different to that for proximal and distal colon cancers (pchisq. =0.02). Our investigation supports a role for XRCC2 in CRC tumorigenesis, conferring susceptibility to rectal tumors.