Open Access Research article

Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County

Qing Da Li1, Hao Li2*, Mei Shu Wang3, Tao Yu Diao4, Zhi Ying Zhou5, Qiang Xue Fang6, Fang Yan Yang7 and Qing Hui Li4

Author Affiliations

1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, 107# Wenhuaxi Road, Jinan, 250012, China

2 Department of Hematology of Tumor Center, Qilu Hospital of Shandong University, 107# Wenhuaxi Road, Jinan, 250012, China

3 Department of Epidemiology, College of Public Health of Shandong University, 104# Wenhuaxi Road, Jinan, 250012, China

4 Department of Epidemiology, Institute of Basic Medicine of Shandong Academy of Medical Sciences, 18877# Jingshi Road, Jinan, 250062,China

5 Department of Statistics, School of Economics, Shandong University, 27# Shada Nanlu, Jinan, 250100,China

6 Department of Infectious Disease of Shandong Center for Disease Control and Prevention, 72# Jingshi Road, Jinan, 250014, China

7 Department of Epidemiology, College of Public Health of Southwestern University, 16# Renminnan Road, Chengdou, 610041, China

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BMC Gastroenterology 2011, 11:74  doi:10.1186/1471-230X-11-74

Published: 14 June 2011



The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.


A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants.


The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 1*1 genotype, the ALDH 2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.


The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.