缺氧诱导因子2α基因多态性与乳腺癌相关性  

Association of Hypoxia-inducible Factor 2α Gene Polymorphisms with Breast Cancer

作　　者：马建萍 宋连川 种生珍 李华 谭丽萍 MA Jian-ping;SONG Lian-chuan;ZHONG Sheng-zhen;LI Hua;TAN Li-ping(The Fifth People’s Hospital of Qinghai Province,Qinghai Province Cancer Hospital,Xining 810007,China)

机构地区：[1]青海省第五人民医院,青海省肿瘤医院,青海西宁810007

出　　处：《肿瘤学杂志》2022年第12期1014-1019,共6页Journal of Chinese Oncology

基　　金：青海省卫健委医药卫生科技项目指导性计划课题(2021-WJZDX-80)

摘　　要：[目的]探讨缺氧诱导因子2α(HIF-2α)基因多态性与乳腺癌的关系。[方法]研究入组2019年1月至2022年1月间在青海省肿瘤医院乳腺科就诊的258例乳腺癌患者和270名健康女性(对照组),研究对象检测4个HIF-2α单核苷酸多态性(rs12619696、rs13419896、rs2881504和rs4953354),分析HIF-2α多态性与乳腺癌易感性之间的关联。使用Kaplan-Meier分析分析来自癌症基因组图谱(TCGA)数据库的1376个乳腺癌样本的总体生存率。[结果]免疫组织化学染色显示,乳腺肿瘤组织标本中的HIF-2α表达高于癌旁组织标本(P<0.05)。TCGA数据集分析显示,HIF-2α高表达乳腺癌患者的总体生存率较低表达显著性降低(P<0.05)。具有CT基因型的HIF-2αrs13419896者患乳腺癌可能性是TT纯合子的2.20倍(AOR=2.20,95%CI:1.70~2.85,P<0.05)。具有HIF-2αrs4953354多态性的C等位基因的女性比具有T等位基因的女性更容易患乳腺癌(AOR=1.29,95%CI:1.06~1.57,P<0.05)。在rs13419896 HIF-2α基因型中,具有CT基因型的患者较具有TT基因型者增加患Ⅲ~Ⅳ期疾病(OR=1.72,95%CI:1.11~2.67)。[结论]HIF-2α基因变异与乳腺癌易感性及其在携带HIF-2αrs13419896多态性女性的乳腺癌进展之间存在关联性。[Objective]To investigate the relationship between the polymorphism of hypoxia-inducible factor 2α(HIF-2α)gene and breast cancer.[Methods]A total of 258 breast cancer patients and 270 healthy women(controls)were recruited from Qinghai Cancer Hospital between January 2019 and January 2022.The HIF-2αSNPs(rs12619696,rs13419896,rs2881504 and rs4953354)were detected with qPCR method.The association between polymorphism of HIF-2αSNPs(rs12619696,rs13419896,rs2881504 and rs4953354)and susceptibility of breast cancer was analyzed.The overall survival of 1376 patients with breast cancer from the Cancer Genome Atlas(TCGA)database30 was analyzed using Kaplan-Meier analysis.[Results]Immunohistochemical staining showed that the expression of HIF-2αin breast cancer tumor tissue samples was higher than that in adjacent tissue samples(P<0.05).TCGA dataset analysis showed that the overall survival rate of breast cancer patients with high HIF-2αexpression was significantly lower than that with low HIF-2αexpression(P<0.05).Compared to TT homozygote of HIF-2αrs13419896,the risk of developing breast cancer in subjects with CT genotype was significantly higher(AOR=2.20,95%CI:1.70~2.85,P<0.05).Compared with T allele,the risk of breast cancer in subjects with the C allele of the HIF-2αrs4953354 polymorphism was higher(AOR=1.29,95%CI:1.06~1.57,P<0.05).Compare with the TT genotype of HIF-2αrs13419896,patients with CT genotype were more likely to develop stageⅢ~Ⅳcancer(OR=1.72,95%CI:1.11~2.67).[Conclusion]There is an association between HIF-2αgene variants and breast cancer susceptibility and HIF-2αrs13419896 polymorphism is associated with breast cancer progression.

关 键 词：缺氧诱导因子2α 乳腺癌 基因多态性 

分 类 号：R737.9[医药卫生—肿瘤]