Abstract

BackgroundThe purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population.MethodsA 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation.ResultsCurrent or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21–4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene–tea drinking: Pinteraction = 0.042; hot beverage/food consumption: Pinteraction = 6.98 × 10−6) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12–3.80).ConclusionsOur findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0156-3) contains supplementary material, which is available to authorized users.

Highlights

  • The purpose of this study was to explore the effects of Cytochrome P450 2C19 (CYP2C19) gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population

  • Increased ESCC risk was associated with smoking, number of pack-years of cigarettes smoked, consumption of pickled vegetables, consumption of hot beverages/food, having a first degree relative with ESCC and having a history of reflux esophagitis

  • We found the frequency of CYP2C19*2 to be higher than that of CYP2C19*3 in Chinese Han subjects and the poor metabolizers (PMs) genotype was associated with an increased risk of ESCC

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Summary

Introduction

The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. Cytochrome P450 2C19 (CYP2C19) is an important phase I enzyme expressed abundantly in endothelial and smooth muscle cells [5,6]. This enzyme is involved in the metabolism of numerous therapeutic drugs and other xenobiotics, including S-mephenytoin, omeprazole, diazepam, proguanil, propranolol and certain antidepressants [7]. It is conceivable that CYP2C19 gene polymorphisms may play a major role in inter-individual variability in drug response, drug–drug and drug–xenobiotic interactions and susceptibility to chemical-induced diseases

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