U2依赖型mRNA剪接体与肝癌的相关性研究

目的 探讨U2依赖型mRNA剪接复合体相关基因多态性与肝癌的风险关联.方法 采用两阶段病例对照研究,筛查阶段采用Openarray中通量分型技术对U2依赖型mRNA剪接复合体的关键基因(U2AF1、U2AF2、SRSF1、SRSF2、SF3B1、SF3A1、SF1和PRPF40)的21个潜在功能标签SNP位点在筛查人群(武汉地区378例新发肝癌病例和461例非肿瘤对照)中进行基因分型;对筛查阶段得到的阳性位点进一步在验证人群(北京地区428例新发肝癌病例和647例非肿瘤对照)中采用TaqMan基因分型技术进行验证.采用加法交互模型分析吸烟/饮酒及遗传因素的交互作用.结果 两阶段人群中均观察到SF3A1基因的rs5994293与肝癌发病风险存在显著关联.合并分析显示,以携带TT基因型者为参照,携带G等位基因者的肝癌发病风险降低30%(OR=0.70,95%CI:0.58～0.84,FDR-P=0.000 5);合并阶段在HBsAg阴性者中观察到吸烟合并饮酒和rs5994293 TT基因型之间存在加法交互作用.结论 携带SF3A1 rs5994293 T等位基因可能增加肝癌发生风险,但仍需大样本研究及功能研究的验证.

Research on the association between U2-dependent spliceosome gene and hepatocellular cancer

Objective To determine the association between U2-dependent spliceosome related 8 key genes and hepatocellular cancer (HCC). Methods A two-stage case-control study was conducted. Twenty-two candidate tag single nucleotide polymorphisms (tagSNPs) were genotyped by TaqMan Openarray assay in a screened population that living in Central China (378 HCC incident cases and 461 controls). Frequencies of 4 SNPs (rs2074733,rs9608886,rs7288947 and rs5994293) showed significant difference between cases and controls in the screened population and then genotyped by TaqMan real-time polymerase chain reaction in the validation Chinese Han population from Beijing(428 cases and 647 controls). Results The rs5994293 in SF3A1 gene showed a significant association with HCC in both screened population and combined population. Subjects with G allele had a lower risk of HCC,compared to those with the TT genotype. OR appeared to be 0.70 (95%CI:0.58-0.84,false discovery rate adjusted P=0.000 5) for the combined population. An additive interaction between smoking,drinking alcohol and rs5994293 TT was observed in HBsAg negative subjects of the combined populations. Conclusion Our results showed an association existing between SF3A1 rs5994293 and HCC. These findings should be confirmed by further independently large-scale population studies and functional analysis.