A potentially functional variant of ARID1B interacts with physical activity in association with risk of hepatocellular carcinoma
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Li Liu1, Nana Tian1, Chengyu Zhou2, Xinqi Lin1, Weibiao Lv3, Zhifeng Lin1, Zibo Lin1, Yongfen Qi1, Yi Yang1, Sidong Chen1, Xinfa Yu2, Yanhui Gao1
1Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
2Department of Oncology, Shunde First People’s Hospital, Foshan, China
3Department of Clinical Laboratory, Shunde First People’s Hospital, Foshan, China
Yanhui Gao, email: firstname.lastname@example.org
Xinfa Yu, email: email@example.com
Keywords: ARID1B, genetic variant, functional annotation, gene-environment interaction, hepatocellular carcinoma
Received: September 06, 2016 Accepted: February 27, 2017 Published: March 10, 2017
The tumor suppressor role of AT-rich interactive domain containing protein 1B (ARID1B) has drawn much attention in area of cancer etiology. However, it had remained unknown whether or not genetic variants of ARID1B involved in development of hepatocellular carcinoma (HCC). In this study, three putatively functional variants in ARID1B (rs73013281C>T, rs167007A>G, and rs9397984C>T) were selected using bioinformatics tools, and a case-control study of 611 cases and 614 controls was conducted to investigate genetic associations with HCC risk in a Southern Chinese population. Two-dimensional gene-environment interactions were also explored using both multiplicative and additive scales. A dominant effect of the rs73013281 was found for HCC risk, with an adjusted odds ratio (OR) of 1.70 [95% confidence interval (CI) = 1.03−2.80] for the CT/TT genotypes compared to the CC genotype. In stratified analysis, the detrimental effect of the T allele on elevated HCC risk was attenuated by physical activity, with an adjusted OR of 2.75 (95% CI = 1.39−5.41) among inactive individuals against that of 0.89 (95% CI = 0.42−1.91) in those who exercised regularly. Expectably, the rs73013281 showed both multiplicative and additive interactions with physical activity (P = 0.037 and 0.006, respectively). In conclusion, these results highlighted the significant genetic contribution of the ARID1B variant, rs73013281, to susceptibility for HCC, especially in interaction with physical activity.
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