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Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas

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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 1–1 3 had a higher risk of each tumor type compared to individuals who had ADH 2–2 3 or ADH 1–2 3 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 1 3 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.

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Acknowledgments

Supported in part by Public Health Service grants ACS CRTG-01-019-01 CCE, U01-CA57983, U01-CA57949, P30ES09089, P30ES10126, and U01-CA57923 and by contracts N02-CP40501 and N01-CN05230 from the American Cancer Society, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. We thank the following: study managers Sarah Greene and Linda Lannom (Westat), data management Shelley Niwa (Westat) and field supervisors Patricia Owens (Connecticut), Tom English (New Jersey), and Berta Nicol-Blades (Washington) for data collection and processing; Qiao Wang for genotyping; the Yale Cancer Center Rapid Case Ascertainment Shared Resource; the 178 hospitals in Connecticut, New Jersey, and Washington for their participation in the study; and the study participants. Certain data used in this study were obtained from the Connecticut Tumor Registry located in the Connecticut Department of Public Health. The authors assume full responsibility for the analyses and interpretation of these data.

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Authors and Affiliations

  1. Mailman School of Public Health, Department of Epidemiology, Columbia University, 722 West 168th Street, Room 724A, New York, NY, 10032, USA

    Mary Beth Terry & Fang Fang Zhang

  2. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Marilie D. Gammon

  3. Department of Epidemiology, Fred Hutchinson Cancer Research Center, Program in Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA

    Thomas L. Vaughan & Janet L. Stanford

  4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA

    Wong-Ho Chow & Joseph F. Fraumeni Jr.

  5. Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA

    Harvey A. Risch & Susan T. Mayne

  6. New Jersey Department of Health and Senior Services, Center for Cancer Initiatives, Trenton, NJ, USA

    Janet B. Schoenberg

  7. AmeriPath New York Gastrointestinal Diagnostics, Shelton, CT, USA

    A. Brian West

  8. Department of Pathology, Columbia University, New York, NY, USA

    Heidi Rotterdam

  9. International Epidemiology Institute, Rockville, MD, USA

    William J. Blot

  10. Vanderbilt University Medical Center, Nashville, TN, USA

    William J. Blot

  11. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA

    Regina M. Santella

Authors
  1. Mary Beth Terry
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  2. Marilie D. Gammon
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  3. Fang Fang Zhang
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  4. Thomas L. Vaughan
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  5. Wong-Ho Chow
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  6. Harvey A. Risch
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  7. Janet B. Schoenberg
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  8. Susan T. Mayne
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  9. Janet L. Stanford
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  10. A. Brian West
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  11. Heidi Rotterdam
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  12. William J. Blot
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  13. Joseph F. Fraumeni Jr.
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  14. Regina M. Santella
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Corresponding author

Correspondence to Mary Beth Terry.

Additional information

Janet B. Schoenberg, Retired.

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Terry, M.B., Gammon, M.D., Zhang, F.F. et al. Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas. Cancer Causes Control 18, 1039–1046 (2007). https://doi.org/10.1007/s10552-007-9046-0

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  • DOI: https://doi.org/10.1007/s10552-007-9046-0

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