HNF1A和HNF1B基因遗传变异与乳腺癌遗传易感性的关联研究  

Genetic polymorphisms in HNF1A and HNF1B are associated with breast cancer susceptibility

作　　者：陈佳萍 周静 蒋涛 江玥 马红霞 CHEN Jiaping;ZHOU Jing;JIANG Tao;JIANG Yue;MA Hongxia(Department of Epidemiology,School of Public Health,Nanjing Medical University,Nanjing 211166;Department of Information,Northern Jiangsu People’s Hospital,Yangzhou 225002;Department of Biostatistics,School of Public Health,Nanjing Medical University,Nanjing 211166,China)

机构地区：[1]南京医科大学公共卫生学院流行病学系,江苏南京211166 [2]苏北人民医院信息处,江苏扬州225002 [3]南京医科大学公共卫生学院生物统计学系,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2022年第2期239-244,251,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(82073639)。

摘　　要：目的:研究肝细胞核因子(hepatocyte nuclear factor 1,HNF)1A和HNF1B基因遗传变异与乳腺癌遗传易感性之间的相关性。方法:采用病例对照研究,选取1032例经病理组织学确诊的乳腺癌患者以及与之相匹配的1063例健康女性对照,应用Illumina基因分型平台对HNF1A和HNF1B基因多态位点进行基因分型检测;在调整年龄、初潮年龄、绝经状态的基础上,通过Logistic回归计算OR值及95%CI,比较不同基因型与乳腺癌发病风险之间的相关性。结果:位于HNF1A基因上的3个位点与中国人群乳腺癌发病风险显著相关,其中包括HNF1A基因外显子区的rs2464196(OR=0.80,95%CI:0.71~0.91,P=7.45×10^(-4)),HNF1A基因内含子区的rs1183910(OR=0.87,95%CI:0.77~0.99,P=0.039)和rs7310409(OR=0.86,95%CI:0.76~0.98,P=0.023)。进一步FDR校正后,rs2464196位点与乳腺癌易感性仍然存在着显著的相关性(P=4.47×10^(-3))。结论:肝细胞核因子HNF1A基因上的rs2464196多态位点可能是中国人群乳腺癌的易感标志物。Objective:We investigated whether genetic variants of HNF1A and HNF1B were associated with the risk of breast cancer in a Chinese Han population.Methods:A case-control study of 1032 breast cancer cases and 1063 cancer-free female controls was performed,and six single nucleotide polymorphisms(SNPs)in HNF1A and HNF1B were genotyped in Illumina genotyping platform.Logistic regression was used to calculate the odds ratios(ORs)and 95%confidence intervals(CIs)for the association between a single locus and breast cancer risk with adjustment for age,age at menarche,and menopausal status.Results:Multiple logistic regression analysis illustrated that three SNPs within HNF1A gene were associated with significantly decreased risk of breast cancer(rs2464196,OR=0.80,95%CI:0.71~0.91,P=7.45×10^(-4);rs1183910,OR=0.87,95%CI:0.77~0.99,P=0.039;rs7310409,OR=0.86,95%CI:0.76~0.98,P=0.023).After correction for multiple comparisons(FDR<0.05),rs2464196 was still significantly associated with susceptibility to breast cancer(P=4.47×10^(-3)).Conclusion:The SNP rs2464196 within HNF1 A gene may be a candidate marker for susceptibility to breast cancer in Chinese Han population.

关 键 词：乳腺癌 HNF1A基因 HNF1B基因 单核苷酸多态性 易感性 

分 类 号：R737.9[医药卫生—肿瘤]