Discipline of Medical Genetic, Faculty of Health, University of Newcastle, NSW, Australia.
Cancer Epidemiol. 2012 Apr;36(2):183-9. doi: 10.1016/j.canep.2011.09.003. Epub 2011 Oct 5.
DNA repair plays a pivotal role in maintaining genomic integrity with over 130 genes involved in various repair pathways that include base excision repair, nucleotide excision repair, double strand break repair and DNA mismatch repair. Polymorphisms within genes that are involved in these processes have been widely reported to be associated with cancer susceptibility in an extensive range of malignancies that include colorectal cancer (CRC). Lynch syndrome is caused by inherited germline mutations in DNA mismatch repair genes, predominantly in MLH1 and MSH2, that predispose to a variety of epithelial malignancies, most notably CRC. Despite being a relatively well understood hereditary cancer syndrome there remain several questions in relation to genetic influences on disease expression. Since Lynch syndrome is associated with a breakdown in DNA mismatch repair variation in other DNA repair genes may influence disease expression. In this report we have genotyped 424 Australian and Polish Lynch syndrome participants for eight common DNA repair gene polymorphisms to assess any association with the age of CRC onset. The DNA repair gene SNPs included in the study were: BRCA2 (rs11571653), MSH3 (rs26279), Lig4 (rs1805386), OGG1 (rs1052133), XRCC1 (rs25487), XRCC2 (rs3218536 and rs1799793) and XRCC3 (rs861539). Cox multi-variant regression modelling failed to provide any convincing evidence of an effect in any of the polymorphisms analysed. The data suggest that polymorphisms in DNA repair genes do not contribute to cancer risk in a population of CRC patients who are at increased risk of disease as a result in a deficiency of DNA mismatch repair.
DNA 修复在维持基因组完整性方面起着关键作用，超过 130 个基因参与各种修复途径，包括碱基切除修复、核苷酸切除修复、双链断裂修复和 DNA 错配修复。广泛报道，这些过程中涉及的基因中的多态性与多种恶性肿瘤（包括结直肠癌）的癌症易感性有关。林奇综合征是由 DNA 错配修复基因中的遗传胚系突变引起的，主要是 MLH1 和 MSH2，易患多种上皮恶性肿瘤，最显著的是结直肠癌。尽管林奇综合征是一种相对了解的遗传性癌症综合征，但与疾病表达相关的遗传影响仍存在一些问题。由于林奇综合征与 DNA 错配修复的破坏有关，其他 DNA 修复基因的变异可能会影响疾病的表达。在本报告中，我们对 424 名澳大利亚和波兰的林奇综合征患者进行了 8 个常见 DNA 修复基因多态性的基因分型，以评估其与结直肠癌发病年龄的关系。研究中包括的 DNA 修复基因 SNP 有：BRCA2（rs11571653）、MSH3（rs26279）、Lig4（rs1805386）、OGG1（rs1052133）、XRCC1（rs25487）、XRCC2（rs3218536 和 rs1799793）和 XRCC3（rs861539）。Cox 多变量回归模型分析未提供任何令人信服的证据表明分析的多态性中有任何影响。该数据表明，在由于 DNA 错配修复缺陷而增加疾病风险的结直肠癌患者群体中，DNA 修复基因中的多态性不会增加癌症风险。
