Skip to main content
SpringerLink
Log in

Genetic–Epidemiological Evidence for the Role of Acetaldehyde in Cancers Related to Alcohol Drinking

  • Conference paper
  • First Online:
Biological Basis of Alcohol-Induced Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 815))

Abstract

Alcohol drinking increases the risk for a number of cancers. Currently, the highest risk (Group 1) concerns oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, as assessed by the International Agency for Research on Cancer (IARC). Alcohol and other beverage constituents, their metabolic effects, and alcohol-related unhealthy lifestyles have been suggested as etiological factors. The aim of the present survey is to evaluate the carcinogenic role of acetaldehyde in alcohol-related cancers, with special emphasis on the genetic–epidemiological evidence. Acetaldehyde, as a constituent of alcoholic beverages, and microbial and endogenous alcohol oxidation well explain why alcohol-related cancers primarily occur in the digestive tracts and other tissues with active alcohol and acetaldehyde metabolism. Genetic–epidemiological research has brought compelling evidence for the causality of acetaldehyde in alcohol-related cancers. Thus, IARC recently categorized alcohol-drinking-related acetaldehyde to Group 1 for head and neck and esophageal cancers. This is probably just the tip of the iceberg, since more recent epidemiological studies have also shown significant positive associations between the aldehyde dehydrogenase ALDH2 (rs671)*2 allele (encoding inactive enzyme causing high acetaldehyde elevations) and gastric, colorectal, lung, and hepatocellular cancers. However, a number of the current studies lack the appropriate matching or stratification of alcohol drinking in the case-control comparisons, which has led to erroneous interpretations of the data. Future studies should consider these aspects more thoroughly. The polymorphism phenotypes (flushing and nausea) may provide valuable tools for future successful health education in the prevention of alcohol-drinking-related cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Newsholme A (1903) The possible association of the consumption of alcohol with excessive mortality from cancer. Br Med J 2241:1529–1531

    Google Scholar 

  2. IARC (2010) Alcohol consumption and ethyl carbamate. IARC Monogr Eval Carcinog Risks Hum 96:1–1424

    Google Scholar 

  3. IARC (2012) personal habits and indoor combustions. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 100E:1–575

    Google Scholar 

  4. Secretan B, Straif K, Baan R et al (2009) A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 10(11):1033–1034

    PubMed  Google Scholar 

  5. Sanchez-Alvarez R, Martinez-Outschoorn UE, Lin Z et al (2013) Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention. Cell Cycle 12(2):289–301. doi:10.4161/cc.23109

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Lieber CS, Baraona E, Leo MA et al (1987) International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 15/2. Metabolism and metabolic effects of ethanol, including interaction with drugs, carcinogens and nutrition. Mutat Res 186(3):201–233

    CAS  PubMed  Google Scholar 

  7. Leo MA, Lieber CS (1999) Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 69(6):1071–1085

    CAS  PubMed  Google Scholar 

  8. Hamid A, Wani NA, Kaur J (2009) New perspectives on folate transport in relation to alcoholism-induced folate malabsorption—association with epigenome stability and cancer development. FEBS J 276(8):2175–2191. doi:10.1111/j.1742-4658.2009.06959

    CAS  PubMed  Google Scholar 

  9. Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92(18):1472–1489

    CAS  PubMed  Google Scholar 

  10. Watson RR, Nixon P, Seitz HK et al (1994) Alcohol and cancer. Alcohol Alcohol Suppl 2:453–455

    CAS  PubMed  Google Scholar 

  11. Singletary KW, Gapstur SM (2001) Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286(17):2143–2151

    CAS  PubMed  Google Scholar 

  12. Stickel F, Schuppan D, Hahn EG et al (2002) Cocarcinogenic effects of alcohol in hepatocarcinogenesis. Gut 51(1):132–139

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Obe G, Ristow H (1979) Mutagenic, cancerogenic and teratogenic effects of alcohol. Mutat Res 65(4):229–259

    CAS  PubMed  Google Scholar 

  14. Obe G, Anderson D, International Commission for Protection against Environmental Mutagens and Carcinogens (1987) ICPEMC Working Paper No. 15/1. Genetic effects of ethanol. Mutat Res 186(3):177–200

    CAS  PubMed  Google Scholar 

  15. Ishikawa H, Yamamoto H, Tian Y et al (2003) Effects of ALDH2 gene polymorphisms and alcohol-drinking behavior on micronuclei frequency in non-smokers. Mutat Res 541(1–2):71–80

    CAS  PubMed  Google Scholar 

  16. Brooks PJ, Theruvathu JA (2005) DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol 35(3):187–93

    CAS  PubMed  Google Scholar 

  17. Balbo S, Meng L, Bliss RL et al (2012) Kinetics of DNA adduct formation in the oral cavity after drinking alcohol. Cancer Epidemiol Biomarkers Prev 21(4):601–8. doi:10.1158/1055-9965

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Soffritti M, Belpoggi F, Lambertin L et al (2002) Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. Ann N Y Acad Sci 982:87–105

    CAS  PubMed  Google Scholar 

  19. Launoy G, Milan C, Day NE et al (1997) Oesophageal cancer in France: potential importance of hot alcoholic drinks. Int J Cancer 71(6):917–923

    CAS  PubMed  Google Scholar 

  20. Linderborg K, Joly JP, Visapää JP et al (2008) Potential mechanism for Calvados-related oesophageal cancer. Food Chem Toxicol 2:476–479

    Google Scholar 

  21. Brooks PJ, Enoch MA, Goldman D et al (2009) The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med 6(3):e50. doi:10.1371/journal.pmed.1000050

    PubMed  Google Scholar 

  22. Eriksson CJP (2001) The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol Clin Exp Res 5 Suppl ISBRA):15S–32S

    Google Scholar 

  23. Li H, Borinskaya S, Yoshimura K et al (2009) Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant. Ann Hum Genet 73(Pt 3):335–345. doi:10.1111/j.1469-1809.2009.00517

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Carr LG, Foroud T, Stewart T et al (2002) Influence of ADH1B polymorphism on alcohol use and its subjective effects in a Jewish population. Am J Med Genet 112(2):138–143

    PubMed  Google Scholar 

  25. Li H, Mukherjee N, Soundararajan U et al (2007) Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia. Am J Hum Genet 81(4):842–846

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Higuchi S (1994) Polymorphisms of ethanol metabolizing enzyme genes and alcoholism. Alcohol Alcohol Suppl 2:29–34

    CAS  PubMed  Google Scholar 

  27. Yokoyama A, Muramatsu T, Ohmori T et al (1996) Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males. Cancer Epidemiol Biomarkers Prev 5(2):99–102

    CAS  PubMed  Google Scholar 

  28. Yokoyama A, Muramatsu T, Ohmori T et al (1996) Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics. Cancer 77(10):1986–1990

    CAS  PubMed  Google Scholar 

  29. Yokoyama A, Ohmori T, Muramatsu T et al (1996) Cancer screening of upper aerodigestive tract in Japanese alcoholics with reference to drinking and smoking habits and aldehyde dehydrogenase-2 genotype. Int J Cancer 68(3):313–316

    CAS  PubMed  Google Scholar 

  30. Hori H, Kawano T, Endo M et al (1997) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility. J Clin Gastroenterol 25(4):568–575

    CAS  PubMed  Google Scholar 

  31. Yokoyama A, Ohmori T, Muramatsu T et al (1998) Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and aldehyde dehydrogenase-2 genotype in Japanese alcoholics. Cancer Epidemiol Biomarkers Prev 7(6):473–476

    CAS  PubMed  Google Scholar 

  32. Yokoyama A, Muramatsu T, Ohmori T et al (1998) Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis 19(8):1383–1387

    CAS  PubMed  Google Scholar 

  33. Tanabe H, Ohhira M, Ohtsubo T et al (1999) Genetic polymorphism of aldehyde dehydrogenase 2 in patients with upper aerodigestive tract cancer. Alcohol Clin Exp Res 23(4 Suppl):17S–20S

    CAS  PubMed  Google Scholar 

  34. Yokoyama A, Muramatsu T, Omori T et al (1999) Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics. Alcohol Clin Exp Res 23(11):1705–1710

    CAS  PubMed  Google Scholar 

  35. Nomura T, Noma H, Shibahara T et al (2000) Aldehyde dehydrogenase 2 and glutathione S-transferase M 1 polymorphisms in relation to the risk for oral cancer in Japanese drinkers. Oral Oncol 36(1):42–46

    CAS  PubMed  Google Scholar 

  36. Muto M, Hitomi Y, Ohtsu A et al (2000) Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients. Gut 47(2):256–261

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Chao YC, Wang LS, Hsieh TY et al (2000) Chinese alcoholic patients with esophageal cancer are genetically different from alcoholics with acute pancreatitis and liver cirrhosis. Am J Gastroenterol 95(10):2958–2964

    CAS  PubMed  Google Scholar 

  38. Yokoyama A, Muramatsu T, Omori T et al (2001) Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics. Carcinogenesis 22(3):433–439

    CAS  PubMed  Google Scholar 

  39. Matsuo K, Hamajima N, Shinoda M et al (2001) Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer. Carcinogenesis 22(6):913–916

    CAS  PubMed  Google Scholar 

  40. Itoga S, Nomura F, Makino Y et al (2002) Tandem repeat polymorphism of the CYP2E1 gene: an association study with esophageal cancer and lung cancer. Alcohol Clin Exp Res 26(8 Suppl):15S–19S

    CAS  PubMed  Google Scholar 

  41. Yokoyama A, Watanabe H, Fukuda H et al (2002) Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. Cancer Epidemiol Biomarkers Prev 9:895–900

    Google Scholar 

  42. Watanabe S, Sasahara K, Kinekawa F et al (2002) Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer. Oncol Rep 9(5):1063–1068

    CAS  PubMed  Google Scholar 

  43. Muto M, Nakane M, Hitomi Y et al (2002) Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer. Carcinogenesis 23(10):1759–1765

    CAS  PubMed  Google Scholar 

  44. Yokoyama A, Kato H, Yokoyama T et al (2002) Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma. Carcinogenesis 23(11):1851–1859

    CAS  PubMed  Google Scholar 

  45. Boonyaphiphat P, Thongsuksai P, Sriplung H et al (2002) Lifestyle habits and genetic susceptibility and the risk of esophageal cancer in the Thai population. Cancer Lett 186(2):193–199

    CAS  PubMed  Google Scholar 

  46. Yokoyama A, Yokoyama T, Muramatsu T et al (2003) Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men. Carcinogenesis 24(11):1773–1778

    CAS  PubMed  Google Scholar 

  47. Yokoyama T, Yokoyama A, Kato H et al (2003) Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for esophageal squamous cell carcinoma in Japanese men. Cancer Epidemiol Biomarkers Prev 12(11 Pt 1):1227–1233

    CAS  PubMed  Google Scholar 

  48. Muto M, Takahashi M, Ohtsu A et al (2005) Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region. Carcinogenesis 26(5):1008–1012

    CAS  PubMed  Google Scholar 

  49. Yokoyama A, Omori T, Yokoyama T et al (2005) Esophageal melanosis, an endoscopic finding associated with squamous cell neoplasms of the upper aerodigestive tract, and inactive aldehyde dehydrogenase-2 in alcoholic Japanese men. J Gastroenterol 40(7):676–684

    PubMed  Google Scholar 

  50. Yang CX, Matsuo K, Ito H et al (2005) Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions. Asian Pac J Cancer Prev 6(3):256–262

    PubMed  Google Scholar 

  51. Wu CF, Wu DC, Hsu HK et al (2005) Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males. World J Gastroenterol 11(33):5103–5108

    CAS  PubMed  Google Scholar 

  52. Yokoyama A, Kato H, Yokoyama T et al (2006) Esophageal squamous cell carcinoma and aldehyde dehydrogenase-2 genotypes in Japanese females. Alcohol Clin Exp Res 30(3):491–500

    PubMed  Google Scholar 

  53. Cai L, You NC, Lu H et al (2006) Dietary selenium intake, aldehyde dehydrogenase-2 and X-ray repair cross-complementing 1 genetic polymorphisms, and the risk of esophageal squamous cell carcinoma. Cancer 106(11):2345–2354

    CAS  PubMed  Google Scholar 

  54. Yokoyama A, Mizukami T, Omori T et al (2006) Melanosis and squamous cell neoplasms of the upper aerodigestive tract in Japanese alcoholic men. Cancer Sci 97(9):905–911

    CAS  PubMed  Google Scholar 

  55. Yokoyama A, Omori T, Yokoyama T et al (2006) Risk of squamous cell carcinoma of the upper aerodigestive tract in cancer-free alcoholic Japanese men: an endoscopic follow-up study. Cancer Epidemiol Biomarkers Prev 15(11):2209–2215

    PubMed  Google Scholar 

  56. Chen YJ, Chen C, Wu DC et al (2006) Interactive effects of lifetime alcohol consumption and alcohol and aldehyde dehydrogenase polymorphisms on esophageal cancer risks. Int J Cancer 119(12):2827–2831

    CAS  PubMed  Google Scholar 

  57. Hashimoto T, Uchida K, Okayama N et al (2006) ALDH2 1510 G/A (Glu487Lys) polymorphism interaction with age in head and neck squamous cell carcinoma. Tumour Biol 27(6):334–338

    CAS  PubMed  Google Scholar 

  58. Yokoyama A, Yokoyama T, Omori T et al (2007) Helicobacter pylori, chronic atrophic gastritis, inactive aldehyde dehydrogenase-2, macrocytosis and multiple upper aerodigestive tract cancers and the risk for gastric cancer in alcoholic Japanese men. J Gastroenterol Hepatol 22(2):210–217

    CAS  PubMed  Google Scholar 

  59. Asakage T, Yokoyama A, Haneda T et al (2007) Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma. Carcinogenesis 28(4):865–874

    CAS  PubMed  Google Scholar 

  60. Hiraki A, Matsuo K, Wakai K et al (2007) Gene-gene and gene-environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan. Cancer Sci 98(7):1087–1091

    CAS  PubMed  Google Scholar 

  61. Yang SJ, Wang HY, Li XQ et al (2007) Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China. World J Gastroenterol 13(43):5760–5764

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Li DP, Dandara C, Walther G et al (2008) Genetic polymorphisms of alcohol metabolising enzymes: their role in susceptibility to oesophageal cancer. Clin Chem Lab Med 46(3):323–328. doi:10.1515/CCLM.2008.073

    CAS  PubMed  Google Scholar 

  63. Guo YM, Wang Q, Liu YZ et al (2008) Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males. World J Gastroenterol 14(9):1444–1449

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Lee CH, Lee JM, Wu DC et al (2008) 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 122(6):1347–1356

    CAS  PubMed  Google Scholar 

  65. Yokoyama A, Omori T, Yokoyama T et al (2008) Risk of metachronous squamous cell carcinoma in the upper aerodigestive tract of Japanese alcoholic men with esophageal squamous cell carcinoma: a long-term endoscopic follow-up study. Cancer Sci 99(6):1164–1171. doi:10.1111/j.1349-7006.2008.00807

    CAS  PubMed  Google Scholar 

  66. Ding JH, Li SP, Cao HX et al (2009) Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males. World J Gastroenterol 15(19):2395–2400

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Lee CH, Wu DC, Wu IC et al (2009) Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis. Int J Cancer 125(5):1134–1142. doi:10.1002/ijc.24357

    CAS  PubMed  Google Scholar 

  68. Cui R, Kamatani Y, Takahashi A et al (2009) Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology 137(5):1768–1775. doi:10.1053/j.gastro.2009.07.070

    CAS  PubMed  Google Scholar 

  69. Ding JH, Li SP, Cao HX et al (2010) Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population. J Hum Genet 55(2):97–102. doi:10.1038/jhg.2009.129

    CAS  PubMed  Google Scholar 

  70. Oze I, Matsuo K, Hosono S et al (2010) Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population. Cancer Sci 101(8):1875–1880. doi:10.1111/j.1349-7006.2010.01599

    CAS  PubMed  Google Scholar 

  71. Oikawa T, Iijima K, Koike T et al (2010) Deficient aldehyde dehydrogenase 2 is associated with increased risk for esophageal squamous cell carcinoma in the presence of gastric hypochlorhydria. Scand J Gastroenterol 45(11):1338–1344. doi:10.3109/00365521.2010.495419

    CAS  PubMed  Google Scholar 

  72. Tanaka F, Yamamoto K, Suzuki S et al (2010) Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles. Gut 59(11):1457–1464. doi:10.1136/gut.2009.205724

    CAS  PubMed  Google Scholar 

  73. Li QD, Li H, Wang MS et al (2011) Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County. BMC Gastroenterol 11:74. doi:10.1186/1471-230X-11-74

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Yokoyama A, Tanaka Y, Yokoyama T et al (2011) p53 protein accumulation, iodine-unstained lesions, and alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes in Japanese alcoholic men with esophageal dysplasia. Cancer Lett 308(1):112–117. doi:10.1016/j.canlet.2011.04.020

    CAS  PubMed  Google Scholar 

  75. Wang Y, Ji R, Wei X, Gu L et al (2011) Esophageal squamous cell carcinoma and ALDH2 and ADH1B polymorphisms in Chinese females. Asian Pac J Cancer Prev 12(8):2065–2068

    PubMed  Google Scholar 

  76. Matsuo K, Rossi M, Negri E et al (2012) Folate, alcohol, and aldehyde dehydrogenase 2 polymorphism and the risk of oral and pharyngeal cancer in Japanese. Eur J Cancer Prev 21(2):193–198. doi:10.1097/CEJ.0b013e32834c9be5

    CAS  PubMed  Google Scholar 

  77. Yokoyama A, Hirota T, Omori T et al (2012) Development of squamous neoplasia in esophageal iodine-unstained lesions and the alcohol and aldehyde dehydrogenase genotypes of Japanese alcoholic men. Int J Cancer 130(12):2949–2960. doi:10.1002/ijc.26296

    CAS  PubMed  Google Scholar 

  78. Katada C, Muto M, Nakayama M et al (2012) Risk of superficial squamous cell carcinoma developing in the head and neck region in patients with esophageal squamous cell carcinoma. Laryngoscope 122(6):1291–1296. doi:10.1002/lary.23249

    PubMed  Google Scholar 

  79. Guo LK, Zhang CX, Guo XF et al (2012) Association of genetic polymorphisms of aldehyde dehydrogenase-2 and cytochrome P450 2E1-RsaI and alcohol consumption with oral squamous cell carcinoma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 34(4):390–395. doi:10.3881/j.issn.1000-503X.2012.04.015

    CAS  PubMed  Google Scholar 

  80. Gu H, Gong D, Ding G et al (2012) A variant allele of ADH1B and ALDH2, is associated with the risk of esophageal cancer. Exp Ther Med 4(1):135–140

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Chung CS, Lee YC, Liou JM et al (2014) Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis. Dis Esophagus 27(5):493–503. doi:10.1111/j.1442-2050.2012.01437

    PubMed  Google Scholar 

  82. Wu C, Kraft P, Zhai K et al (2012) Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet 44(10):1090–1097. doi:10.1038/ng.2411

    CAS  PubMed  Google Scholar 

  83. Wu M, Chang SC, Kampman E et al (2013) Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer 132(8):1868–1877. doi:10.1002/ijc.27803

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Bye H, Prescott NJ, Matejcic M et al (2011) Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa. Carcinogenesis 32(12):1855–1861. doi:10.1093/carcin/bgr211

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Tian D, Feng Z, Hanley NM et al (1998) Multifocal accumulation of p53 protein in esophageal carcinoma: evidence for field cancerization. Int J Cancer 78(5):568–575

    CAS  PubMed  Google Scholar 

  86. Katoh T, Kaneko S, Kohshi K et al (1999) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer. Int J Cancer 83(5):606–609

    CAS  PubMed  Google Scholar 

  87. Ji YB, Tae K, Ahn TH et al (2011) Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans. Exp Mol Med 41(11):772–781. doi:10.3858/emm.2009.41.11.083

    Google Scholar 

  88. Zhou YZ, Diao YT, Li H et al (2010) Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia. World J Gastroenterol 16(27):3445–3449

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Gao Y, He Y, Xu J et al (2013) Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population. Hum Genet 132(6):649–656. doi:10.1007/s00439-013-1276-5

    CAS  PubMed  Google Scholar 

  90. Hashibe M, Boffetta P, Zaridze D et al (2006) Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract. Cancer Epidemiol Biomarkers Prev 15(4):696–703

    CAS  PubMed  Google Scholar 

  91. McKay JD, Truong T, Gaborieau V et al (2011) A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genet 7(3):e1001333. doi:10.1371/journal.pgen.1001333

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Hakenewerth AM, Millikan RC, Rusyn I et al (2011) Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 20(11):2438–49. doi:10.1158/1055-9965.EPI-11-0649

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Dickson PA, James MR, Heath AC et al (2006) Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity, consumption, and dependence in Europeans. Alcohol Clin Exp Res 30(7):1093–1100

    CAS  PubMed  Google Scholar 

  94. Ma WJ, Lv GD, Zheng ST et al (2010) DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China. World J Gastroenterol 16(5):641–647

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Brennan P, Lewis S, Hashibe M et al (2004) Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review. Am J Epidemiol 159(1):1–16

    PubMed  Google Scholar 

  96. Yokoyama A, Tsutsumi E, Imazeki H et al (2007) Contribution of the alcohol dehydrogenase-1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men. Int J Cancer 121(5):1047–1054

    CAS  PubMed  Google Scholar 

  97. Matsuo K, Oze I, Hosono S et al (2013) The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer. Carcinogenesis 34(7):1510–1515. doi:10.1093/carcin/bgt080

    CAS  PubMed  Google Scholar 

  98. Nan HM, Park JW, Song YJ et al (2005) Kimchi and soybean pastes are risk factors of gastric cancer. World J Gastroenterol 11(21):3175–3181

    CAS  PubMed  Google Scholar 

  99. Nan HM, Song YJ, Yun HY et al (2005) Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer. World J Gastroenterol 11(25):3834–3841

    CAS  PubMed  Google Scholar 

  100. Shin CM, Kim N, Cho SI et al (2011) Association between alcohol intake and risk for gastric cancer with regard to ALDH2 genotype in the Korean population. Int J Epidemiol 40(4):1047–1055. doi:10.1093/ije/dyr067

    PubMed  Google Scholar 

  101. You WC, Hong JY, Zhang L et al (2005) Genetic polymorphisms of CYP2E1, GSTT1, GSTP1, GSTM1, ALDH2, and ODC and the risk of advanced precancerous gastric lesions in a Chinese population. Cancer Epidemiol Biomarkers Prev 14(2):451–458

    CAS  PubMed  Google Scholar 

  102. Cao HX, Li SP, Wu JZ et al (2010) Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for stomach cancer in Chinese males. Asian Pac J Cancer Prev 11(4):1073–1077

    PubMed  Google Scholar 

  103. Zhang FF, Hou L, Terry MB et al (2007) Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland. Int J Cancer 121(9):2060–2064

    CAS  PubMed  Google Scholar 

  104. Duell EJ, Sala N, Travier N et al (2012) Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Carcinogenesis 33(2):361–367. doi:10.1093/carcin/bgr285

    CAS  PubMed  Google Scholar 

  105. Chiang CP, Jao SW, Lee SP et al (2012) Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer. Alcohol 46(1):37–49. doi:10.1016/j.alcohol.2011.08.004

    CAS  PubMed  Google Scholar 

  106. Matsuo K, Hamajima N, Hirai T et al (2002) Aldehyde dehydrogenase 2 (ALDH2) genotype affects rectal cancer susceptibility due to alcohol consumption. J Epidemiol 12(2):70–76

    PubMed  Google Scholar 

  107. Murata M, Tagawa M, Watanabe S et al (1999) Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients. Jpn J Cancer Res 90(7):711–719

    CAS  PubMed  Google Scholar 

  108. Yin G, Kono S, Toyomura K et al (2007) Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study. Cancer Sci 98(8):1248–1253

    CAS  PubMed  Google Scholar 

  109. Otani T, Iwasaki M, Hanaoka T et al (2005) Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan. Nutr Cancer 53(1):42–50

    CAS  PubMed  Google Scholar 

  110. Miyasaka K, Hosoya H, Tanaka Y et al (2010) Association of aldehyde dehydrogenase 2 gene polymorphism with pancreatic cancer but not colon cancer. Geriatr Gerontol Int 10(Suppl 1):S120–6. doi:10.1111/j.1447-0594.2010.00616

    PubMed  Google Scholar 

  111. Matsuo K, Wakai K, Hirose K et al (2006) A gene-gene interaction between ALDH2 Glu487Lys and ADH2 His47Arg polymorphisms regarding the risk of colorectal cancer in Japan. Carcinogenesis 27(5):1018–1023

    CAS  PubMed  Google Scholar 

  112. Yang H, Zhou Y, Zhou Z et al (2009) A novel polymorphism rs1329149 of CYP2E1 and a known polymorphism rs671 of ALDH2 of alcohol metabolizing enzymes are associated with colorectal cancer in a southwestern Chinese population. Cancer Epidemiol Biomarkers Prev 18(9):2522–2527. doi:10.1158/1055-9965

    CAS  PubMed  Google Scholar 

  113. Kuriki K, Hamajima N, Chiba H et al (2005) Relation of the CD36 gene A52C polymorphism to the risk of colorectal cancer among Japanese, with reference to with the aldehyde dehydrogenase 2 gene Glu487Lys polymorphism and drinking habit. Asian Pac J Cancer Prev 6(1):62–68

    PubMed  Google Scholar 

  114. Gao CM, Takezaki T, Wu JZ et al (2008) Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males. World J Gastroenterol 14(32):5078–5083

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Landi S, Gemignani F, Moreno V et al (2005) A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer. Pharmacogenet Genomics 15(8):535–546

    CAS  PubMed  Google Scholar 

  116. Ferrari P, McKay JD, Jenab M et al (2012) Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study. Eur J Clin Nutr 66(12):1303–1308. doi:10.1038/ejcn.2012.173

    CAS  PubMed  Google Scholar 

  117. Miyasaka K, Kawanami T, Shimokata H et al (2005) Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among smokers in a Japanese male population. Pancreas 30(2):95–98

    CAS  PubMed  Google Scholar 

  118. Kanda J, Matsuo K, Suzuki T et al (2009) Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese. Cancer Sci 100(2):296–302. doi:10.1111/j.1349-7006.2008.01044

    CAS  PubMed  Google Scholar 

  119. Kato S, Tajiri T, Matsukura N et al (2003) Genetic polymorphisms of aldehyde dehydrogenase 2, cytochrome p450 2E1 for liver cancer risk in HCV antibody-positive Japanese patients and the variations of CYP2E1 mRNA expression levels in the liver due to its polymorphism. Scand J Gastroenterol 38(8):886–893

    CAS  PubMed  Google Scholar 

  120. Tomoda T, Nouso K, Sakai A et al (2012) Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study. J Gastroenterol Hepatol 27(4):797–804. doi:10.1111/j.1440-1746.2011.06948

    PubMed  Google Scholar 

  121. Sakamoto T, Hara M, Higaki Y et al (2006) Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. Int J Cancer 118(6):1501–1507

    CAS  PubMed  Google Scholar 

  122. Munaka M, Kohshi K, Kawamoto T et al (2003) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol 129(6):355–360

    CAS  PubMed  Google Scholar 

  123. Ding J, Li S, Wu J et al (2008) Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk of primary hepatocellular carcinoma in a Chinese population. Asian Pac J Cancer Prev 9(1):31–35

    CAS  PubMed  Google Scholar 

  124. Takeshita T, Yang X, Inoue Y et al (2000) Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese. Cancer Lett 149(1–2):69–76

    CAS  PubMed  Google Scholar 

  125. Koide T, Ohno T, Huang XE et al (2000) HBV/HCV infection, alcohol, tobacco and genetic polymorphisms for hepatocellular carcinoma in Nagoya, Japan. Asian Pac J Cancer Prev 1(3):239–245

    Google Scholar 

  126. Yu SZ, Huang XE, Koide T et al (2002) Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China. Jpn J Cancer Res 93(12):1287–1292

    CAS  PubMed  Google Scholar 

  127. Shibata A, Fukuda K, Nishiyori A et al (1998) A case-control study on male hepatocellular carcinoma based on hospital and community controls. J Epidemiol 8(1):1–5

    CAS  PubMed  Google Scholar 

  128. Ohhira M, Fujimoto Y, Matsumoto A et al (1996) Hepatocellular carcinoma associated with alcoholic liver disease: a clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2. Alcohol Clin Exp Res 20(9 Suppl):378A–382A

    CAS  PubMed  Google Scholar 

  129. Yamagishi Y, Horie Y, Kajihara M (2004) Hepatocellular carcinoma in heavy drinkers with negative markers for viral hepatitis. Hepatol Res 28(4):177–183

    CAS  PubMed  Google Scholar 

  130. Minegishi Y, Tsukino H, Muto M et al (2007) Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite-related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population. Cancer 110(2):353–362

    CAS  PubMed  Google Scholar 

  131. Eom SY, Zhang YW, Kim SH et al (2009) Influence of NQO1, ALDH2, and CYP2E1 genetic polymorphisms, smoking, and alcohol drinking on the risk of lung cancer in Koreans. Cancer Causes Control 20(2):137–145. doi:10.1007/s10552-008-9225-7

    PubMed  Google Scholar 

  132. Park JY, Matsuo K, Suzuki T et al (2010) Impact of smoking on lung cancer risk is stronger in those with the homozygous aldehyde dehydrogenase 2 null allele in a Japanese population. Carcinogenesis 31(4):660–665. doi:10.1093/carcin/bgq021

    CAS  PubMed  Google Scholar 

  133. Zienolddiny S, Campa D, Lind H et al (2008) A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers. Carcinogenesis 29(6):1164–1169. doi:10.1093/carcin/bgn020

    CAS  PubMed  Google Scholar 

  134. Choi JY, Abel J, Neuhaus T et al (2003) Role of alcohol and genetic polymorphisms of CYP2E1 and ALDH2 in breast cancer development. Pharmacogenetics 13(2):67–72

    CAS  PubMed  Google Scholar 

  135. Kawase T, Matsuo K, Hiraki A et al (2009) Interaction of the effects of alcohol drinking and polymorphisms in alcohol-metabolizing enzymes on the risk of female breast cancer in Japan. J Epidemiol 19(5):244–250

    PubMed Central  PubMed  Google Scholar 

  136. Sangrajrang S, Sato Y, Sakamoto H et al (2010) Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case-control study in Thai women. Breast Cancer Res Treat 123(3):885–893. doi:10.1007/s10549-010-0804-4

    CAS  PubMed  Google Scholar 

  137. Ribas G, Milne RL, Gonzalez-Neira A (2008) Haplotype patterns in cancer-related genes with long-range linkage disequilibrium: no evidence of association with breast cancer or positive selection. Eur J Hum Genet 16(2):252–60

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work has been supported by the Magnus Ehrnrooth Foundation and the Liv och Hälsa medical association.

Author information

Authors and Affiliations

  1. Department of Public Health, Hjelt Institute, University of Helsinki, Mannerheimintie, 172, 00014, Helsinki, Finland

    C. J. Peter Eriksson Ph.D.

  2. Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, 30, 00271, Helsinki, Finland

    C. J. Peter Eriksson Ph.D.

Authors
  1. C. J. Peter Eriksson Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. J. Peter Eriksson Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the United States, Washington, District of Columbia, USA

    Samir Zakhari

  3. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz

  4. Department of Pathology, Anatomy, & Cell, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jan B. Hoek

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this paper

Cite this paper

Eriksson, C.J.P. (2015). Genetic–Epidemiological Evidence for the Role of Acetaldehyde in Cancers Related to Alcohol Drinking. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_3

Download citation

Publish with us

Policies and ethics

Search

Navigation