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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.    Electronic supplementary material  The online version of this article (10.1186/s12885-018-4551-y) contains supplementary material, which is available to authorized users.

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