Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Esophageal Cancer | Research article

Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study

Authors: Chang Kyun Choi, Jungho Yang, Sun-Seog Kweon, Sang-Hee Cho, Hye-Yeon Kim, Eun Myung, Min-Ho Shin

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Background

Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population.

Methods

This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer.

Results

Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34–3.23) and 0.08 (95% CI: 0.00–0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43–6.34) and 6.18 (95% CI: 1.40–19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption.

Conclusion

In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.
Literature
1.
go back to reference Griswold MG, Fullman N, Hawley C, Arian N, Zimsen SRM, Tymeson HD, et al. Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2018;392:1015–35.CrossRef Griswold MG, Fullman N, Hawley C, Arian N, Zimsen SRM, Tymeson HD, et al. Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2018;392:1015–35.CrossRef
2.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef
3.
go back to reference Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer. 2015;112:580–93.CrossRef Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer. 2015;112:580–93.CrossRef
5.
go back to reference Millwood IY, Walters RG, Mei XW, Guo Y, Yang L, Bian Z, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. Lancet. 2019;393:1831–42.CrossRef Millwood IY, Walters RG, Mei XW, Guo Y, Yang L, Bian Z, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. Lancet. 2019;393:1831–42.CrossRef
6.
go back to reference Quillen EE, Chen XD, Almasy L, Yang F, He H, Li X, et al. ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample. Am J Med Genet Part B Neuropsychiatr Genet. 2014;165:103–10.CrossRef Quillen EE, Chen XD, Almasy L, Yang F, He H, Li X, et al. ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample. Am J Med Genet Part B Neuropsychiatr Genet. 2014;165:103–10.CrossRef
7.
go back to reference Takeuchi F, Isono M, Nabika T, Katsuya T, Sugiyama T, Yamaguchi S, et al. Confirmation of ALDH2 as a major locus of drinking behavior and of its variants regulating multiple metabolic phenotypes in a Japanese population. Circ J. 2011;75:911–8.CrossRef Takeuchi F, Isono M, Nabika T, Katsuya T, Sugiyama T, Yamaguchi S, et al. Confirmation of ALDH2 as a major locus of drinking behavior and of its variants regulating multiple metabolic phenotypes in a Japanese population. Circ J. 2011;75:911–8.CrossRef
9.
go back to reference Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, et al. Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde Dehydrogenase-2 genotype. Alcohol Clin Exp Res. 2008;32:1607–14.CrossRef Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, et al. Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde Dehydrogenase-2 genotype. Alcohol Clin Exp Res. 2008;32:1607–14.CrossRef
10.
go back to reference Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, et al. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal Cancer risk. Gastroenterology. 2009;137:1768–75.CrossRef Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, et al. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal Cancer risk. Gastroenterology. 2009;137:1768–75.CrossRef
11.
go back to reference Suo C, Yang Y, Yuan Z, Zhang T, Yang X, Qing T, et al. Alcohol intake interacts with functional genetic polymorphisms of aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH) to increase esophageal squamous cell Cancer risk. J Thorac Oncol. 2019;14:712–25.CrossRef Suo C, Yang Y, Yuan Z, Zhang T, Yang X, Qing T, et al. Alcohol intake interacts with functional genetic polymorphisms of aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH) to increase esophageal squamous cell Cancer risk. J Thorac Oncol. 2019;14:712–25.CrossRef
12.
go back to reference Yu C, Guo Y, Bian Z, Yang L, Millwood IY, Walters RG, et al. Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: a population-based cohort study. Int J Cancer. 2018;143:1652–61.CrossRef Yu C, Guo Y, Bian Z, Yang L, Millwood IY, Walters RG, et al. Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: a population-based cohort study. Int J Cancer. 2018;143:1652–61.CrossRef
13.
go back to reference Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, et al. Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int J Cancer. 2008;122:1347–56.CrossRef Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, et al. Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int J Cancer. 2008;122:1347–56.CrossRef
14.
go back to reference Gao Y, He Y, Xu J, Xu L, Du J, Zhu C, et al. Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population. Hum Genet. 2013;132:649–56.CrossRef Gao Y, He Y, Xu J, Xu L, Du J, Zhu C, et al. Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population. Hum Genet. 2013;132:649–56.CrossRef
15.
go back to reference Wu M, Chang SC, Kampman E, Yang J, Wang XS, Gu XP, et al. Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 2013;132:1868–77.CrossRef Wu M, Chang SC, Kampman E, Yang J, Wang XS, Gu XP, et al. Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 2013;132:1868–77.CrossRef
16.
go back to reference Kweon SS, Shin MH, Jeong SK, Nam HS, Lee YH, Park KS, et al. Cohort profile: the Namwon study and the dong-gu study. Int J Epidemiol. 2014;43:558–67.CrossRef Kweon SS, Shin MH, Jeong SK, Nam HS, Lee YH, Park KS, et al. Cohort profile: the Namwon study and the dong-gu study. Int J Epidemiol. 2014;43:558–67.CrossRef
17.
go back to reference Choi CK, Kweon S-S, Cho S-H, Kim H-Y, Shin M-H. Association between ALDH2 polymorphism and gastric Cancer risk in a Korean population. J Korean Med Sci. 2020;35:e148.CrossRef Choi CK, Kweon S-S, Cho S-H, Kim H-Y, Shin M-H. Association between ALDH2 polymorphism and gastric Cancer risk in a Korean population. J Korean Med Sci. 2020;35:e148.CrossRef
18.
go back to reference Zhong H, Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol. 2015;4:193–9.CrossRef Zhong H, Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol. 2015;4:193–9.CrossRef
19.
go back to reference Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al. The functional ALDH2 polymorphism is associated with breast cancer risk: a pooled analysis from the breast Cancer association consortium. Mol Genet Genomic Med. 2019;7:e707.CrossRef Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al. The functional ALDH2 polymorphism is associated with breast cancer risk: a pooled analysis from the breast Cancer association consortium. Mol Genet Genomic Med. 2019;7:e707.CrossRef
20.
go back to reference Väkeväinen S, Tillonen J, Agarwal DP, Srivastava N, Salaspuro M. High salivary acetaldehyde after a moderate dose of alcohol in ALDH2- deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol Clin Exp Res. 2000;24:873–7.CrossRef Väkeväinen S, Tillonen J, Agarwal DP, Srivastava N, Salaspuro M. High salivary acetaldehyde after a moderate dose of alcohol in ALDH2- deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol Clin Exp Res. 2000;24:873–7.CrossRef
21.
go back to reference IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt E):1–538.PubMedCentral IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt E):1–538.PubMedCentral
22.
go back to reference Matsuda T, Matsumoto A, Uchida M, Kanaly RA, Misaki K, Shibutani S, et al. Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. Carcinogenesis. 2007;28:2363–6.CrossRef Matsuda T, Matsumoto A, Uchida M, Kanaly RA, Misaki K, Shibutani S, et al. Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. Carcinogenesis. 2007;28:2363–6.CrossRef
23.
go back to reference Yukawa Y, Muto M, Hori K, Nagayoshi H, Yokoyama A, Chiba T, et al. Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics. Cancer Sci. 2012;103:1651–5.CrossRef Yukawa Y, Muto M, Hori K, Nagayoshi H, Yokoyama A, Chiba T, et al. Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics. Cancer Sci. 2012;103:1651–5.CrossRef
24.
go back to reference Hendershot CS, Otto JM, Collins SE, Liang T, Wall TL. Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2. Ann Behav Med. 2010;40:77–88.CrossRef Hendershot CS, Otto JM, Collins SE, Liang T, Wall TL. Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2. Ann Behav Med. 2010;40:77–88.CrossRef
Metadata
Title
Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study
Authors
Chang Kyun Choi
Jungho Yang
Sun-Seog Kweon
Sang-Hee Cho
Hye-Yeon Kim
Eun Myung
Min-Ho Shin
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07993-4

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine