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World J Gastroenterol. Dec 7, 2008; 14(45): 6986-6992
Published online Dec 7, 2008. doi: 10.3748/wjg.14.6986
Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population
Jiang-Mei Qin, Lei Yang, Bo Chen, Xiu-Mei Wang, Feng Li, Pei-Hua Liao, Lin He
Jiang-Mei Qin, Lei Yang, Bo Chen, Xiu-Mei Wang, Feng Li, Pei-Hua Liao, Lin He, Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi 832002, Xinjiang Uygur Autonomous Region, China
Author contributions: Qin JM, Yang L and Li F designed the research; Qin JM analyzed the data and wrote the manuscript; Chen B, Wang XM, Liao PH and He L performed the research.
Supported by The National Natural Science Foundation of China, No. 30660161; Prophase Basic Research Project of Ministry of Science and Technology of China, No. 2005CCA03700, No. 2007CB516804; Science and Technology Research Project of Ministry of Education of China, No. 206167; Laboratory of Endemic and Ethnic Diseases Program of Xinjiang, No. 200416
Correspondence to: Jiang-Mei Qin, Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, 2nd North Road, Shihezi 832002, Xinjiang Uygur Autonomous Region, China. qinjiangmei@yahoo.com.cn
Telephone: +86-933-2057153 Fax: +86-933-2057153
Received: August 25, 2008
Revised: October 25, 2008
Accepted: November 1, 2008
Published online: December 7, 2008
Abstract

AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CYP4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China.

METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 population- or hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis.

RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502E1C1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502E1C1/C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone.

CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.

Keywords: Kazakh; Esophageal Cancer; Methylenetetrahydrofolate reductase C677T; Cytochrome P4502E1; Genetic polymorphism; Environment risk factors; Interaction; Case control study