一种罕见的 CHD5 单倍型及其与环境因素的相互作用预测肝细胞癌风险。

A rare CHD5 haplotype and its interactions with environmental factors predicting hepatocellular carcinoma risk.

机构信息

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China.

Department of Blood Transfusion, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

BMC Cancer. 2018 Jun 15;18(1):658. doi: 10.1186/s12885-018-4551-y.

DOI:10.1186/s12885-018-4551-y

PMID:29907144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6003142/

Abstract

BACKGROUND

CHD5 is a conventional tumour-suppressing gene in many tumours. The aim of this study was to determine whether CHD5 variants contribute to the risk of hepatocellular carcinoma (HCC).

METHODS

Gene variants were identified using next-generation sequencing targeted on referenced mutations followed by TaqMan genotyping in two case-control studies.

RESULTS

We discovered a rare variant (haplotype AG) in CHD5 (rs12564469-rs9434711) that was markedly associated with the risk of HCC in a Chinese population. A logistical regression model and permutation test confirmed the association. Indeed, the association quality increased in a gene dose-dependent manner as the number of samples increased. In the stratified analysis, this haplotype risk effect was statistically significant in a subgroup of alcohol drinkers. The false-positive report probability and multifactor dimensionality reduction further supported the finding.

CONCLUSIONS

Our results suggest that the rare CHD5 gene haplotype and alcohol intake contribute to the risk of HCC. Our findings can be valuable to researchers of cancer precision medicine looking to improve diagnosis and treatment of HCC.

摘要

背景

CHD5 是许多肿瘤中的传统抑癌基因。本研究旨在确定 CHD5 变异是否会增加肝细胞癌（HCC）的风险。

方法

通过靶向参考突变的下一代测序，结合 TaqMan 基因分型，在两项病例对照研究中鉴定基因变异。

结果

我们在中国人群中发现了 CHD5 中的罕见变异（单倍型 AG）（rs12564469-rs9434711）与 HCC 的风险显著相关。逻辑回归模型和置换检验证实了这种关联。事实上，随着样本数量的增加，关联质量呈基因剂量依赖性增加。在分层分析中，该单倍型风险效应在饮酒亚组中具有统计学意义。假阳性报告概率和多因素降维进一步支持了这一发现。