CAJ | 학술논문

目的研究显示核苷酸切除修复通路在去除吸烟引起的DNA损伤中发挥着重要的作用,旨在探讨核苷酸切除修复通路单核苷酸多态性与吸烟相关性肺癌易感性的关系.方法选取1 010例肺癌患者和1 011例止常对照.采用基于通路的候选基因选点策略,从核苷酸切除修复通路相关的8个核心基因中筛选出40个标签SNPs进行检测和分析.结果单个位点分析发现6个SNPs(ERCC1 2个,DDB2 2个,ERCCA/XPF 1个,XPC 1个)与肺癌的易感性相关.进一步采用Logistic回归模型,调整年龄、性别、吸烟史和肿瘤家族史后,仍有3个SNPs(ERCC1 rs3212948,DDB2 rs830083,ERCC4 rs3136038)与肺癌易感性存在统计学关联.等位基因联合分析结果进一步表明肺癌的发病风险随着风险等位基因个数的增加而增加,尤其是ERCC1,ERCC2,ERCC3,ERCC5,XPA和XPC.结论本研究结果提示核苷酸切除修复通路基因多态性可能与中国汉族人群的肺癌个体易感性有关,值得进一步进行功能学探讨及大样本人群验证.
목적 연구현시핵감산절제수복통로재거제흡연인기적DNA손상중발휘착중요적작용,지재탐토핵감산절제수복통로단핵감산다태성여흡연상관성폐암역감성적관계.방법 선취1 010례폐암환자화1 011례지상대조.채용기우통로적후선기인선점책략,종핵감산절제수복통로상관적8개핵심기인중사선출40개표첨SNPs진행검측화분석.결과 단개위점분석발현6개SNPs(ERCC1 2개,DDB2 2개,ERCCA/XPF 1개,XPC 1개)여폐암적역감성상관.진일보채용Logistic회귀모형,조정년령、성별、흡연사화종류가족사후,잉유3개SNPs(ERCC1 rs3212948,DDB2 rs830083,ERCC4 rs3136038)여폐암역감성존재통계학관련.등위기인연합분석결과 진일보표명폐암적발병풍험수착풍험등위기인개수적증가이증가,우기시ERCC1,ERCC2,ERCC3,ERCC5,XPA화XPC.결론 본연구결과 제시핵감산절제수복통로기인다태성가능여중국한족인군적폐암개체역감성유관,치득진일보진행공능학탐토급대양본인군험증.
The nucleotide excision repair (NER) pathway plays an important role in removal of tobaccocaused DNA lesions.and single nucleotide polymorphisms(SNPs) of the genes in this pathway are good candidates for investigating susceptibility to smoking-related lung cancer.Using a pathway-based candidate gene strategy,we selected 40 tagging SNPs of 8 core NER genes in a case-control study of 1010 incident lung cancer patients and 1011 cancer-free controls in a Chinese population.Six SNPs (2 in ERCC1,2 in DDB2,1 in ERCCA/XPF and 1 in XPC) were associated with lung csncer risk in the single locus analysis.In the lngistic regression model,3(ERCC1 rs3212948,DDB2 rs830083 and ERCCA rs3136038) of these SNPs remain significant predictors for lung cancer risk.In the allele-combined analyses,the risk of lung cancer was significantly,increased as the numbers of risk alleles increased for ERCC1,ERCC2,ERCC3,ERCC5,XPA,and XPC as well as for all genes combined.These results from the pathway-based SNPs association study in this Chinese population provide further evidence to support those genetic variants in the NER pathway may jointly contribute to individual susceptibilitv to lung cancer.