Impact of NOTCH1 polymorphisms on liver cancer in a Chinese Han population

NOTCH1, a member of the Notch family, is up-expression in advanced liver cancer (LC) patients and is associated with tumor sizes, tumor stage, metastasis, and invasion. A few studies have discovered the contribution of NOTCH1 variants to LC risk. Our purpose was to assess the relationship of NOTCH1 rs10521, rs2229971, and rs4489420 to LC risk. We enrolled 709 LC patients and 708 healthy controls. Genotyping was determined through the Agena MassARRAY system. Multiple genetic models by logistic regression were useful for odds ratios (ORs) with 95% confidence intervals (CIs). Rs10521-G (p = 0.009, OR = 0.75, 95% CI: 0.61–0.93), rs2229971-A (p = 0.023, OR = 0.81, 95% CI: 0.67–0.97), and rs4489420-A (p = 0.014, OR = 0.38, 95% CI: 0.16–0.85) might be protective factors for LC occurrence in the Chinese Han population, especially rs10521 and rs2229971 (false-positive report probability (FPRP) 90%). Interestingly, stratified analysis displayed that the contribution of NOTCH1 polymorphisms to LC risk might be associated with gender, age, smoking, and drinking. Our data first determined that NOTCH1 rs10521-G, rs2229971-A, and rs4489420-A might be protective factors for LC susceptibility.NOTCH1基因（NOTCH1）作为Notch家族成员，在晚期肝癌（liver cancer, LC）患者中呈过表达状态，且与肿瘤大小、临床分期、肿瘤转移及侵袭行为显著相关。已有少量研究探明了NOTCH1基因变异与肝癌发病风险的关联。本研究旨在探讨NOTCH1基因rs10521、rs2229971及rs4489420位点多态性与肝癌发病风险的相关性。本研究共纳入709例肝癌患者与708例健康对照个体，采用Agena MassARRAY系统完成基因型检测。通过logistic回归分析构建多种遗传模型，计算比值比（odds ratio, OR）及其95%置信区间（confidence interval, CI）。研究结果显示，在中国汉族人群中，rs10521-G（p=0.009，OR=0.75，95%CI：0.61~0.93）、rs2229971-A（p=0.023，OR=0.81，95%CI：0.67~0.97）及rs4489420-A（p=0.014，OR=0.38，95%CI：0.16~0.85）可能为肝癌发病的保护因素，其中rs10521与rs2229971的假阳性报告概率（false-positive report probability, FPRP）为90%。有趣的是，分层分析结果显示，NOTCH1基因多态性与肝癌发病风险的关联可能受性别、年龄、吸烟及饮酒状态的影响。本研究首次证实，NOTCH1基因rs10521-G、rs2229971-A及rs4489420-A位点多态性可能是肝癌易感性的保护因素。