CAJ | 학술논문

目的探讨DNA修复基因多态性与中国南方汉族人群散发性结直肠癌发病的相关性,验证多因子降维法(MDR)应用于多因子疾病基因-基因、基因-环境交互作用分析的可行性.方法采用自然人群为基础的病例对照研究设计,运用PCR-RFLP方法对206例结直肠癌病例和845例正常对照开展OGG1 Ser326Cys,XRCC1 Arg194Trp、Arg280His和Arg399Gln,XPD Lys751Gln和XRCC3 Thr241Met等DNA修复体系常见单核苷酸多态性(SNP)的检测分型.结果个体特征与结直肠癌的关联分析表明,年龄与结直肠癌的发病正相关,高年龄组(≥61岁)与低年龄组(≥42岁至＜61岁)相比,结直肠癌患病风险增高有统计学意义(校正OR=2.04,95%CI:1.49～2.80);家族肿瘤史同样与结直肠癌的发病存在有统计学意义的正相关关系(校正OR=1.51,95%CI:1.05～2.17).前述各SNP的等位基因和基因型分布频率在正常对照组和病例组间差异均无统计学意义(P＞0.05).采用MDR对基因-基因、基因-环境交互作用模型的筛选分析表明,最佳的交互作用模型包含了年龄分布、饮酒史、XRCC1 Arg194Trp和OGG1 Ser326Cys等4个因子(平均检验准确度=0.616,交叉验证一致性=10/10,P=0.011);进一步以筛选出的低风险组合为参照,logistic拟合分析发现高风险组合可以使结直肠癌的患病风险增高并有统计学意义(OR=2.72,95%CI:1.66～4.47).结论 DNA修复基因多态性对中国人散发性结直肠癌风险的遗传影响符合低外显性特征,并与环境因子可能存在着复杂的联合作用.
목적 탐토DNA수복기인다태성여중국남방한족인군산발성결직장암발병적상관성,험증다인자강유법(MDR)응용우다인자질병기인-기인、기인-배경교호작용분석적가행성.방법 채용자연인군위기출적병례대조연구설계,운용PCR-RFLP방법대206례결직장암병례화845례정상대조개전OGG1 Ser326Cys,XRCC1 Arg194Trp、Arg280His화Arg399Gln,XPD Lys751Gln화XRCC3 Thr241Met등DNA수복체계상견단핵감산다태성(SNP)적검측분형.결과 개체특정여결직장암적관련분석표명,년령여결직장암적발병정상관,고년령조(≥61세)여저년령조(≥42세지＜61세)상비,결직장암환병풍험증고유통계학의의(교정OR=2.04,95%CI:1.49～2.80);가족종류사동양여결직장암적발병존재유통계학의의적정상관관계(교정OR=1.51,95%CI:1.05～2.17).전술각SNP적등위기인화기인형분포빈솔재정상대조조화병례조간차이균무통계학의의(P＞0.05).채용MDR대기인-기인、기인-배경교호작용모형적사선분석표명,최가적교호작용모형포함료년령분포、음주사、XRCC1 Arg194Trp화OGG1 Ser326Cys등4개인자(평균검험준학도=0.616,교차험증일치성=10/10,P=0.011);진일보이사선출적저풍험조합위삼조,logistic의합분석발현고풍험조합가이사결직장암적환병풍험증고병유통계학의의(OR=2.72,95%CI:1.66～4.47).결론 DNA수복기인다태성대중국인산발성결직장암풍험적유전영향부합저외현성특정,병여배경인자가능존재착복잡적연합작용.
Objective To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. Methods In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown.Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis.Results As compared to the younger age group (≥42,＜61 years), the risk of colorectal cancer in older age group (≥61 years) increased significantly ( OR = 2.04,95% CI: 1.49-2.80). Similar result was observed in the family cancer history ( OR = 1.51, 95% CI : 1.05-2.17 ). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0. 616, P=0.011 ). Using a logistic regression model, the"high-risk"individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model ( OR = 2.72,95% CI : 1.66-4.47 ). Conclusion The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.