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

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

Qin Xiao  1   2 , Lianzhou Chen  3 , Haiqing Luo  1   4 , Hongmei Li  1   5 , Qingming Kong  6 , Fei Jiao  7 , Shifeng Pang  1 , Ming Zhang  8 , Feifei Lan  9 , Wenguo Fan  10 , Hui Luo  11 , Tao Tao  12 , Xiao Zhu  13
Affiliations

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

Qin Xiao et al. BMC Cancer. .

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.

Keywords: Alcohol intake; CHD5; Gene haplotype; Hepatocellular carcinoma; Risk.

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Conflict of interest statement

Ethics approval and consent to participate

The ethics committee of Guangdong Medical University authorised the experimental and research protocols of this study. All procedures performed in studies were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All controls and and patients (or relatives of patients who already died) provided written informed consent.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CHD5 LD mapping and analysis in the discovery study. a LD mapping. b Manhattan plot. The –log10P values were for the association of each SNP with HCC, from two-sided Cochran–Armitage tests for trend. c 105 permutation tests for the association analysis. d and e Q-Q plots for the test statistics of observed Chi-square values against expected Chi-square values (E, removing rs9434741)
See this image and copyright information in PMC

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