在中国的队列对肝癌的危险环境因素和KIF1B遗传变异体之间的

StephenW

World J Gastroenterol. 2016 Apr 28; 22(16): 4183–4190.
Published online 2016 Apr 28.   doi:  10.3748/wjg.v22.i16.4183


PMCID: PMC4837435




Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohortJun-Hu Chen, Yan-Yan Wang, Wei-Biao Lv, Yu Gan, Wei Chang, Na-Na Tian, Xiao-Hui Huang, Li Liu, Xin-Fa Yu, and  Si-Dong Chen

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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.

StephenW

世界今日医学Gastroenterol。 2016年04月28日; 22（16）：4183-4190。
2016年在网上发布四月28 DOI：10.3748 / wjg.v22.i16.4183
PMCID：PMC4837435
在中国的队列对肝癌的危险环境因素和KIF1B遗传变异体之间的相互作用的影响
君胡琛，阎焱王炜吕彪，俞甘，魏畅，娜娜天，小黄晖，李刘昕发玉，和Si-东辰
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目的：研究KIF1B变种（rs17401966和rs3748578）和环境因素之间潜在的相互作用对肝细胞癌（HCC）的在中国处于高风险区域的风险的影响。

方法：三106例肝癌和居住在广东省顺德区306医院为基础的控制的参与者，中国的患者。临床特性通过审查从患者的档案的完整医疗史收集，并用一个问卷和临床检查收集的流行病学数据。两个单核苷酸多态性KIF1B（rs17401966和rs3748578）的（单核苷酸多态性）被选为当前的研究。所有受试者使用TaqMan TM实时聚合酶链反应分型。乘性和加逻辑回归模型被用来评估各种基因与环境的相互作用。

结果：吸烟，淡水鱼生，乙型肝炎病毒（HBV）感染与肝癌家族史的频繁消费是重要的危险因素，肝癌在这个人口。乙肝病毒慢性感染是肝癌[比值比（OR）= 12.02最重要的环境危险因素; 95％置信区间（95％CI）：6.02-24.00]。没有显著的关联被发现之间的KIF1B单独变种和肝癌的风险。然而，rs17401966和酒精消费（P为添加剂相互作用= 0.0382）之间观察到显著加性效应修饰。携带任何rs17401966的AG或GG基因型不饮酒者相比，个人列为酒精消费者rs17401966的AA基因型有显著增加肝癌的危险性（OR = 2.36; 95％CI：1.49-3.74）。

结论：KIF1B rs17401966变异与饮酒之间的基因 - 环境的相互作用可能有助于肝癌在中国的个人发展。
关键词：肝癌，驱动蛋白家族成员1B，环境因素，饮酒，基因 - 环境的相互作用

核心提示：KIF1B已被提议作为一个有前途的易感基因肝细胞癌（HCC）在中国人群最近的全基因组关联分析（GWAS）。然而，在该GWAS最显著变体（rs17401966），得到在随后的重复研究的结果不一致。在这项工作中，我们评估遗传易感性HCC和基因与环境相互作用rs17401966的作用。我们的研究表明，KIF1B rs17401966变异与饮酒之间的基因 - 环境的相互作用显著有助于肝癌在中国人口的发展。