Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: A population‐based case–control study in China

• Published in: International journal of cancer Vol. 132; no. 8; pp. 1868 - 1877
• Main Authors: Wu, Ming, Chang, Shen‐Chih, Kampman, Ellen, Yang, Jie, Wang, Xu‐Shan, Gu, Xiao‐Ping, Han, Ren‐Qiang, Liu, Ai‐Min, Wallar, Gina, Zhou, Jin‐Yi, Kok, Frans J., Zhao, Jin‐Kou, Zhang, Zuo‐Feng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2013; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Aged; alcohol; Alcohol dehydrogenase; alcohol dehydrogenase (ADH); Alcohol Dehydrogenase - genetics; Alcohol use; aldehyde dehydrogenase (ALDH); Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase, Mitochondrial; aldehyde dehydrogenases; associations; Biological and medical sciences; Cancer; Case-Control Studies; China; consumption; Dehydrogenases; drinking; Esophageal cancer; Esophageal Neoplasms - epidemiology; Esophageal Neoplasms - genetics; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Humans; japanese; Male; Medical research; Medical sciences; metabolism; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide; Population Surveillance; Risk factors; single nucleotide polymorphism (SNP); Smoking; squamous-cell carcinoma; Tumors; variants; Asia; China; Genetic variability; esophageal cancer; Esophageal disease; Alcohol dehydrogenase; Case control study; aldehyde dehydrogenase (ALDH); Epidemiology; Esophagus cancer; Alcoholic beverage; Cancerology; Gene; Genetics; Public health; alcohol; Ethanol; Enzyme; ); Genotype; Malignant tumor; Statistical study; alcohol dehydrogenase (ADH); Aldehyde dehydrogenase (NAD; single nucleotide polymorphism (SNP); Digestive diseases; Oxidoreductases; Single nucleotide polymorphism; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.27803

Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population‐based case–control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08–1.66] for G‐allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A‐allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12–2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54–1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high‐risk Chinese population. What's new? Alcohol consumption is considered a major risk factor for esophageal cancer. Previous studies have identified single nucleotide polymorphisms in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with this type of cancer. The authors report an association between ADH1B (rs1229984) with esophageal cancer independent of alcohol drinking and tobacco smoking status. In addition, they find statistical interactions between alcohol drinking and another polymorphism, ALDH2 (rs671) in the Chinese population. These results shed new light onto the complex genetic interactions that exist between alcohol consumption and ADH and ALDH polymorphisms in esophageal cancer.