Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.
BACKGROUND
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.


METHODS
A 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.


RESULTS
Current 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: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80).


CONCLUSIONS
Our 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.
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, China. fmuxe@163.com.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center of Molecular Medicine, Fujian Medical University, Fujian, China. fmuxe@163.com.
Xian-E
XE
Peng
CDC of XiaMen, 681-685Shengguang Road, Xiamen, China. Cfh276@163.com.
Hua-Fang
HF
Chen
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, China. hzj99955888@126.com.
Zhi-Jian
ZJ
Hu
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, China. fydsxs@163.com.
Xi-Shun
XS
Shi
D044466:Asian People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004777:Environment; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D065731:Cytochrome P-450 CYP2C19