nach oben

Erschienen in:

01.11.2007 | Original Paper

Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas

verfasst von: Mary Beth Terry, Marilie D. Gammon, Fang Fang Zhang, Thomas L. Vaughan, Wong-Ho Chow, Harvey A. Risch, Janet B. Schoenberg, Susan T. Mayne, Janet L. Stanford, A. Brian West, Heidi Rotterdam, William J. Blot, Joseph F. Fraumeni Jr., Regina M. Santella

Erschienen in: Cancer Causes & Control | Ausgabe 9/2007

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk.

Methods

We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls).

Results

Individuals homozygous for ADH ₃ ^1–1 had a higher risk of each tumor type compared to individuals who had ADH ₃ ^2–2 or ADH ₃ ^1–2 genotype (OR = 1.7, 95% CI = 1.0–2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7–4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5–5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH ₃ ¹ allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor.

Conclusion

These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas.

Food, Nutrition and the Prevention of Cancer: a Global Perspective. (1997) American Institute for Cancer Research, Washington, DC

Longnecker MP (1994) Alcohol consumption and risk of cancer in humans: an overview. Alcohol 12:87–96CrossRef

Thomas DB (1995) Alcohol as a cause of cancer. Environ Health Perspect 103:153–160PubMedCrossRef

Rothman KJ (1995) Research and prevention priorities for alcohol carcinogenesis. Environ Health Perspect 103:161–163PubMedCrossRef

Kabot GC, Ng SKC, Wynder EL (1993) Tobacco, alcohol intake, and diet in relation to adenocarcinoma of the esophagus and gastric cardia. Cancer Causes Control 4:123–132CrossRef

Garidou A, Tzonou A, Lipworth L, Signorello LB, Kalapothaki V (1996) Life-style factors and medical conditions in relation to esophageal cancer by histologic type in a low-risk population. Int J Cancer 68:295–299PubMedCrossRef

Brown LM, Silverman DT, Pottern LM, Schoenberg JB, Greenberg RS, Swanson GM, Liff JM, Schwartz AG, Hayes RB, Blot WJ, Hoover RN (1994) Adenocarcinoma of the esophagus and esophagogastric junction in white men in the United States: alcohol, tobacco, and socioeconomic factors. Cancer Causes Control 1994:333–340CrossRef

Vaughn TL, Davis S, Kristal A, Thomas DB (1995) Obestity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 4:85–92

Zhang ZF, Kurtz RC, Sun M, Karpeh M, Yu GP, Gargon N, Fein JS, Georgopoulos SK, Harlap S (1996) Adenocarcinomas of the esophagus and gastric cardia: medical conditions, tobacco, alcohol, and socioeconomic factors. Cancer Epidemiol Biomarkers Prev 5:761–768PubMed

10.

Gammon MD, Schoenberg JB, Ahsan H, Risch HA, Vaughan TL, Chow WH, Rotterdam H, West AB, Dubrow R, Stanford JL, Mayne ST, Farrow DC, Niwa S, Blot WJ, Fraumeni JF (1997) Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 89:1277–1284PubMedCrossRef

11.

Lindblad M, Rodriguez LA, Lagergren J (2005) Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study. Cancer Causes Control 16:285–294PubMedCrossRef

12.

Wu AH, Wan P, Bernstein L (2001) A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States). Cancer Causes Control 12:721–732PubMedCrossRef

13.

Devesa SS, Blot WJ, Fraumeni JFJ (1998) Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83:2049–2053PubMedCrossRef

14.

Garro AJ, Lieber CS (1990) Alcohol and cancer. Annu Rev Pharmacol Toxicol 30:219–249PubMedCrossRef

15.

Homann N, Jousimies-Somer H, Jokelainen K, Heine R, Salaspuro M (1997) High aceltaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Carcinogenesis 18:1739–1743PubMedCrossRef

16.

Day CP, Bashir R, James OFW, Bassendine MF, Crabb DW, Thomasson HR, Li TK, Edenberg HJ (1991) Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. Hepatology 14:798–801PubMedCrossRef

17.

Thomasson HR, Crabb DW, Edenberg HJ, Li TK (1993) Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behav Genet 23:131–136PubMedCrossRef

18.

Bosron WF, Crabb DW, Li TK (1983) Relationship between kinetics of liver alcohol dehydrogenase and alcohol metabolism. Pharmacol Biochem Behav 18(Suppl 1):223–227PubMedCrossRef

19.

Bosron WF, Lumeng L, Li TK (1988) Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. Mol Aspects Med 10:147–158PubMedCrossRef

20.

Crabb DW, Matsumoto M, Chang D, You M (2004) Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc 63:49–63PubMedCrossRef

21.

Brennan P, Lewis S, Hashibe M, Bell DA, Boffetta P, Bouchardy C, Caporaso N, Chen C, Coutelle C, Diehl SR, Hayes RB, Olshan AF, Schwartz SM, Sturgis EM, Wei Q, Zavras AI, Benhamou S (2004) Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE Review. Am J Epidemiol 159:1–16PubMedCrossRef

22.

Chen X, Levine L, Kwok PY (1999) Fluorescence polarization in homogeneous nucleic acid analysis. Genome Res 9:492–498PubMed

23.

Daniel WW (1991) Biostatistics: a foundation for analysis in the health sciences. Probability and mathematical statistics-applied. John Wiley & Sons, New York

24.

Hosmer DW, Lemeshow S (1989) Applied logistic regression. John Wiley & Sons, New York

25.

Rothman KJ, Greenland S (1998) Modern epidemiology. Lippincott-Raven, Philadelphia

26.

Yokoyama A, Omori T (2003) Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. Jpn J Clin Oncol 33:111–121PubMedCrossRef

27.

Yokoyama A, Kato H, Yokoyama T, Tsujinaka T, Muto M, Omori T, Haneda T, Kumagai Y, Igaki H, Yokoyama M, Watanabe H, Fukuda H, Yoshimizu H (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 23:1851–1859PubMedCrossRef

28.

Yang CX, Matsuo K, Ito H, Shinoda M, Hatooka S, Hirose K, Wakai K, Saito T, Suzuki T, Maeda T, Tajima K (2005) Gene-environment interactions between alcohol drinking and the MTHFR C677T polymorphism impact on esophageal cancer risk: results of a case-control study in Japan. Carcinogenesis 26:1285–1290PubMedCrossRef

29.

Smith GD, Ebrahim S (2004) Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 34:481–482

30.

Lewis SJ, Smith GD (2005) Alcohol, ALDH2, and esophageal cancer: a meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev 14:1967–1971PubMedCrossRef

Titel: Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas
verfasst von: Mary Beth Terry
Marilie D. Gammon
Fang Fang Zhang
Thomas L. Vaughan
Wong-Ho Chow
Harvey A. Risch
Janet B. Schoenberg
Susan T. Mayne
Janet L. Stanford
A. Brian West
Heidi Rotterdam
William J. Blot
Joseph F. Fraumeni Jr.
Regina M. Santella
Publikationsdatum: 01.11.2007
Verlag: Springer Netherlands
Erschienen in: Cancer Causes & Control / Ausgabe 9/2007
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-007-9046-0

Springer Medizin

Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas