Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort

World J Gastroenterol. 2016 Apr 28;22(16):4183-90. doi: 10.3748/wjg.v22.i16.4183.

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

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / ethnology
  • Asian People / genetics
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / ethnology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Chi-Square Distribution
  • China
  • Female
  • Gene Frequency
  • Gene-Environment Interaction*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Kinesins / genetics*
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • KIF1B protein, human
  • Kinesins