错配修复基因多态性与中国人群肺癌发病风险及预后的相关性
Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men.
机构信息
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China; State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.
出版信息
Cancer Epidemiol. 2013 Dec;37(6):917-22. doi: 10.1016/j.canep.2013.08.003. Epub 2013 Sep 5.
PURPOSE
Translesion DNA synthesis (TLS) plays an important role in promoting replication through DNA lesions. Genetic polymorphisms in TLS genes may have potential roles in lung cancer development in humans.
METHODS
We evaluated the association between genetic variants in six TLS genes and the risk and survival of lung cancer in a case-control study in China. Included in the study are 224 lung cancer patients and 448 healthy controls.
RESULTS
Carriers of the G allele of POLκ rs5744724 had significantly reduced risk of lung cancer (odds ratio (OR)=0.62, 95% confidence interval (CI): 0.44-0.89), comparing with those carrying the C allele, and the AA genotype of PCNA rs25406 was also associated with significantly decreased cancer risk compared with the major homozygote alleles (OR=0.47, 95% CI: 0.25-0.86). Haplotype analysis showed that subjects with the POLκ C-G (rs5744533-rs5744724) haplotype had decreased risk of lung cancer (OR=0.69, 95% CI: 0.49-0.98), comparing with those carrying the C-C haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were independent prognostic factors for lung cancer survival with hazard radio (HR) 1.54 (95% CI: 1.12-2.12) and 1.44 (95% CI: 1.06-1.97) respectively.
CONCLUSIONS
Our findings suggested that genetic variants in POLκ and PCNA genes may play roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung cancer survival in Chinese men.
目的
跨损伤 DNA 合成（TLS）在促进 DNA 损伤部位的复制中起着重要作用。TLS 基因的遗传多态性可能在人类肺癌的发生中发挥潜在作用。
方法
我们在中国的病例对照研究中评估了六个 TLS 基因中的遗传变异与肺癌风险和生存的关系。该研究纳入了 224 名肺癌患者和 448 名健康对照者。
结果
与携带 C 等位基因的个体相比，携带 POLκ rs5744724 的 G 等位基因的个体患肺癌的风险显著降低（比值比（OR）=0.62，95%置信区间（CI）：0.44-0.89），PCNA rs25406 的 AA 基因型也与癌症风险显著降低相关（OR=0.47，95%CI：0.25-0.86）。单体型分析显示，与携带主要纯合子单体型的个体相比，携带 POLκ C-G（rs5744533-rs5744724）单体型的个体患肺癌的风险降低（OR=0.69，95%CI：0.49-0.98）。此外，REV1 rs3087386 和 rs3792136 的杂合子是肺癌生存的独立预后因素，危险比（HR）分别为 1.54（95%CI：1.12-2.12）和 1.44（95%CI：1.06-1.97）。
结论
我们的研究结果表明，POLκ 和 PCNA 基因中的遗传变异可能与肺癌的易感性有关，而 REV1 基因可能与中国男性肺癌的生存有关。
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