HOTAIR遗传变异及基因-环境交互作用与肝癌临床特征的关联性分析

Association of HOTAIR genetic variation and gene-environment interaction with clinical features of liver cancer

目的探讨长链非编码RNA HOX转录反义RNA(LncRNA HOTAIR)遗传变异及基因-环境交互作用与肝癌预后相关临床特征的关系。方法选取广东省南方医科大学顺德医院2010年10月-2016年10月收治的原发性肝癌新发患者923例,采用TaqMan荧光定量PCR技术检测HOTAIR rs17105613 T> C、rs12427129 C> T和rs3816153 G> T基因型。采用χ^2检验分析肝癌临床特征分布的差异,应用logistic回归模型分析HOTAIR遗传变异对肝癌TNM分期、门静脉癌栓和发病年龄的影响。结果校正环境因素后,隐性遗传模式下rs17105613和rs3816153与肝癌TNM分期均有统计学关联(P值均<0.05),且rs12427129与吸烟对肝癌发病年龄存在统计学意义的相乘交互作用(P=0.029)和临界统计学意义的相加交互作用(P=0.092)。结论 HOTAIR rs17105613和rs3816153可能与肝癌TNM分期有关,rs12427129与吸烟交互作用可能对肝癌发病年龄有影响,因此HOTAIR遗传变异可能促进肝癌细胞的侵袭和转移。

Objective To investigate the association of the genetic variation of the long non-coding RNA HOX transcript antisense RNA(HOATIR) and gene-environment interaction with prognosis-related clinical features of liver cancer.Methods A total of 923 patients with primary liver cancer Shunde Hospital of Southern Medical University were admitted to a hospital from October 2010 to October 2016 were enrolled in this study.TaqMan quantitative PCR was used to detect HOTAIR rs17105613 T > C,rs12427129 C > T,and rs3816153 G> T genotypes.The chi-square test was used to analyze the difference in the distribution of clinical features of liver cancer,and the logistic regression model was used to analyze the influence of the genetic variation of HOTAIR on the TNM stage of liver cancer,portal vein tumor thrombus,and age of onset.Results After the adjustment for environmental factors,rs17105613 and rs3816153 were significantly associated with TNM stage in the recessive mode(P < 0.05),and there was a statistically significant multiplicative interaction between rs12427129 and smoking on the age of onset of liver cancer(P = 0.029),as well as an additive interaction with critical statistical significance(P = 0.092).Conclusion HOTAIR rs17105613 and rs3816153 may be associated with TNM stage of liver cancer.The interaction between rs12427129 and smoking may influence the age of onset of liver cancer.Therefore,the genetic variation of HOTAIR may promote the invasion and metastasis of hepatoma cells.