SMAD7基因座与中国汉族人群肝细胞癌风险及临床病理发展相关。

SMAD7 loci contribute to risk of hepatocellular carcinoma and clinicopathologic development among Chinese Han population.

作者信息

Ji Jiansong, Xu Min, Zhao Zhongwei, Tu Jianfei, Gao Jun, Lu Chenying, Song Jingjing, Chen Weiqian, Chen Minjiang, Fan Xiaoxi, Cheng Xingyao, Lan Xilin, Li Jie

机构信息

Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, Zhejiang, P.R. China.

Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated with Capital Medical University, Beijing, P.R. China.

出版信息

Oncotarget. 2016 Apr 19;7(16):22186-92. doi: 10.18632/oncotarget.8065.

DOI:10.18632/oncotarget.8065

PMID:26989026

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5008354/

Abstract

Genome-wide association studies (GWAS) have identified three loci at 18q21 (rs4939827, rs7240004, and rs7229639), which maps to SMAD7 loci, were associated with risk of diseases of the digestive system. However, their associations with hepatocellular carcinoma (HCC) risk remain unknown. A case-control study was conducted to assess genetic associations with HCC risk and clinicopathologic development among Chinese Han population. Three SNPs were genotyped among 1,000 HCC cases and 1,000 controls using Sequenom Mass-ARRAY technology. We observed statistically significant associations for the three SMAD7 loci and HCC risk. Each copy of minor allele was associated with a 1.24-1.36 fold increased risk of HCC. We also found that significant differences were observed between rs4939827 and clinical TNM stage and vascular invasion, as well as rs7240004 and vascular invasion. We also established a genetic risk score (GRS) by summing the risk alleles. The GRS was significantly associated with increased risk of HCC and vascular invasion. Our data revealed the SMAD7 loci is associated with HCC susceptibility and its clinicopathologic development.

摘要

全基因组关联研究（GWAS）已确定位于18q21的三个基因座（rs4939827、rs7240004和rs7229639），该区域定位于SMAD7基因座，与消化系统疾病风险相关。然而，它们与肝细胞癌（HCC）风险的关联尚不清楚。我们进行了一项病例对照研究，以评估中国汉族人群中基因与HCC风险及临床病理发展的关联。使用Sequenom Mass-ARRAY技术对1000例HCC病例和1000例对照进行了三个单核苷酸多态性（SNP）的基因分型。我们观察到三个SMAD7基因座与HCC风险之间存在统计学上的显著关联。每一个次要等位基因拷贝都与HCC风险增加1.24至1.36倍相关。我们还发现，rs4939827与临床TNM分期和血管侵犯之间、以及rs7240004与血管侵犯之间存在显著差异。我们还通过对风险等位基因求和建立了遗传风险评分（GRS）。GRS与HCC风险增加和血管侵犯显著相关。我们的数据表明，SMAD7基因座与HCC易感性及其临床病理发展相关。