Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2016; 22(16): 4183-4190
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4183
Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort
Jun-Hu Chen, Yan-Yan Wang, Wei-Biao Lv, Yu Gan, Wei Chang, Na-Na Tian, Xiao-Hui Huang, Li Liu, Xin-Fa Yu, Si-Dong Chen
Jun-Hu Chen, Wei Chang, Si-Dong Chen, Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Jun-Hu Chen, Li Liu, Yu Gan, Wei Chang, Na-Na Tian, Xiao-Hui Huang, Si-Dong Chen, Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, Guangdong Province, China
Yan-Yan Wang, Department of Obstetrics and Gynecology, Affiliated HouJie Hospital of Guangdong Medical College, Dongguan 523945, Guangdong Province, China
Wei-Biao Lv, Xin-Fa Yu, Department of Oncology, The First People’s Hospital of Shunde, Foshan 528300, Guangdong Province, China
Author contributions: Chen JH and Liu L analyzed the data and wrote the manuscript; Chang W, Tian NN, and Lv WB collected materials and clinical data; Wang YY, Gan Y, and Huang XH performed the experiments; Yu XF and Chen SD conceived and designed the study.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the First People’s Hospital of Shunde, Foshan, China.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this work.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at chensidong1@126.com.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Si-Dong Chen, Professor, Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, Guangdong Province, China. chensidong1@126.com
Telephone: +86-20-34055180 Fax: +86-20-34055355
Received: December 25, 2015
Peer-review started: December 28, 2015
First decision: December 30, 2015
Revised: January 17, 2016
Accepted: February 20, 2016
Article in press: February 23, 2016
Published online: April 28, 2016
Processing time: 115 Days and 19.5 Hours
Abstract

AIM: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China.

METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.

RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74).

CONCLUSION: The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.

Keywords: Hepatocellular carcinoma; Kinesin family member 1B; Environmental factors; Alcohol drinking; Gene-environment interaction

Core tip:KIF1B has been proposed as a promising susceptibility gene for hepatocellular carcinoma (HCC) by a recent genome-wide association study (GWAS) in Chinese populations. However, the most significant variant (rs17401966) in this GWAS yielded inconsistent results in subsequent replication studies. In this work, we evaluated the role of rs17401966 in genetic susceptibility to HCC and gene-environment interactions. Our study demonstrates that the gene-environment interaction between the KIF1B rs17401966 variant and drinking alcohol significantly contributed to the development of HCC in the Chinese population.