Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China.
BACKGROUND
Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China.


METHODS
A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques.


RESULTS
Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22-6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05).


CONCLUSIONS
Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China.
Wang
Zemin
Z
Department of Environmental Toxicology and the Institute of Environmental and Human Health, Texas Tech University Lubbock, Texas, USA. zemin.wang@tiehh.ttu.edu <zemin.wang@tiehh.ttu.edu>
Tang
Lili
L
Sun
Guiju
G
Tang
Yuntian
Y
Xie
Yin
Y
Wang
Shaokang
S
Hu
Xu
X
Gao
Weimin
W
Cox
Stephen B
SB
Wang
Jia-Sheng
JS
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D002681:China; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors
D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006899:Mixed Function Oxygenases; C585496:CYP1B1 protein, human; C585710:CYP2A6 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human