ERCC1及其重叠基因3’端非编码区多态性与结直肠癌发病风险关联的病例对照研究

A case control study on ERCC13’UTR polymorphisms,its overlapping genes,and the risk of colorectal cancer

目的探讨切除修复交叉互补基因1(ERCC1)及其重叠基因CD3EAP、PPP1R13L的3’端非编码区(3’UTR)单核苷酸多态性(SNP)与结直肠癌(CRC)发病风险的关联性。方法根据最小等位基因频率(MAF)及样本量确定候选SNP位点。收集200例CRC患者(病例组)和200名健康对照受试者(对照组),利用非条件logistic回归模型分析靶基因候选SNP位点与CRC的关联。结果ERCC1基因SNP位点rs3212986与CRC发生风险相关,与rs3212986 CC基因型相比,AA基因型携带者患CRC的风险增高(P<0.05);将病例组和对照组按性别和年龄分层后,男性或年龄≥60岁人群中AA基因型会增加CRC的患病风险(P<0.05)。单体型分析结果表明,与其他单体型相比,ERCC1单体型AAG发生CRC的风险较高(P<0.05);携带rs3212986、rs2336219、rs735482、rs1007616区域单体型结构CCAC、AAGC、CAGT患CRC风险程度高于野生型(P<0.05)。结论ERCC1 rs3212986位点AA基因型在CRC病例中的出现频率高于对照,其A等位基因会增加CRC的患病风险。ERCC1单体型AAG与CRC的易感性相关。19q13区域单体型结构CCAC、AAGC、CAGT与CRC易感性相关,可能增加CRC的患病风险。

Objective To investigate the association between single nucleotide polymorphisms(SNPs)in the ERCC13’-untranslated region(3’UTR)as well as ERCC1 overlapping genes(CD3EAP and PPP1R13L)and the risk of colorectal cancer(CRC).Methods Candidate SNPs were determined according to the minimum allele frequency(MAF)and sample size.A total of 200 CRC cases and 200 healthy controls were recruited for this study.The association between target gene candidate SNPs and CRC risk was analyzed using an unconditional logistic regression model.Results We found that the SNP rs3212986 of ERCC1 could be linked with an increased risk of CRC.Compared to the CC genotype,the AA genotype of ERCC1 rs3212986 was found to be a high-risk factor for CRC(P<0.05).In particular,stratified by sex and age in CRC cases and controls,the AA genotype of ERCC1 rs3212986 also exhibited an enhanced risk of developing CRC in males or individuals≥50 years of age(P<0.05).Haplotype analysis results revealed that compared with others,the ERCC1 haplotype AAG was linked to a higher risk of CRC(P<0.05).rs3212986,rs2336219,rs735482,and rs1007616 regional haplotype structures CCAC,AAGC,and CAGT showed a higher risk compared to their wild-type counterparts(P<0.05).Conclusion Our findings suggest that the distribution frequency of the ERCC1 rs3212986 AA genotype in CRC cases is higher than that in the control group,and its A allele is associated with an increased risk of CRC.ERCC1 haplotype AAG is correlated with susceptibility to CRC.Regional haplotype structures CCAC,AAGC,and CAGT in 19q13 may increase susceptibility to CRC.