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Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression

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Abstract

A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case–control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined whether the risk associated with cigarette smoking, body mass index (BMI), gastroesophageal reflux disease (GERD), and non-steroidal anti-inflammatory drug (NSAID) use varied by P53 overexpression. We defined P53 overexpression through immunohistochemistry of paraffin-embedded tumor tissues, using cutpoints based on percent of cells positive. Polytomous logistic regression was used to assess differences between each case group (defined by tumor subtype and P53 expression) and the control group by risk factors. The proportion of cases overexpressing P53 by tumor subtype was 72% for esophageal adenocarcinoma, 69% for gastric cardia adenocarcinoma, 52% for non-cardia gastric adenocarcinoma, and 67% for esophageal squamous cell carcinoma. For most tumor subtypes, we found little difference in risk factors by tumor P53 overexpression. For non-cardia gastric cancer however, an association with cigarette smoking was suggested for tumors that do not overexpress P53, whereas larger BMI was related to adenocarcinomas that overexpress P53 versus no overexpression. Overall, this study did not find a clear relationship between P53 protein overexpression and the known risk factors for subtypes of esophageal and gastric cancers. Further research on these tumors is needed to identify molecular markers associated with variations in the risk factor profiles.

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Acknowledgments

Jonine Figueroa would like to thank the Cancer Prevention Fellowship Program, Office of Preventive Oncology, NCI, DHHS for their support. We thank the following: data manager Shelley Niwa (Westat) and field supervisors Patricia Owens (Connecticut), Tom English (New Jersey), and Berta Nicol-Blades (Washington) for data collection and processing; 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. Supported in part by Public Health Service grants U01-CA57983 (M.D. Gammon), U01-CA57049 (T.L. Vaughan), and U01-CA57923 (H.A. Risch) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The work was supported in part by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jonine D. Figueroa, Joseph F. Fraumeni Jr. & Wong-Ho Chow

  2. Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jonine D. Figueroa

  3. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

    Mary Beth Terry & Fang-Fang Zhang

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

    Marilie D. Gammon

  5. Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Thomas L. Vaughan

  6. Department of Epidemiology, School of Public Health & Community Medicine, University of Washington, Seattle, WA, USA

    Thomas L. Vaughan

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

    Harvey A. Risch, Robert Dubrow & Susan T. Mayne

  8. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    David E. Kleiner

  9. Department of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA, 91010, USA

    William P. Bennett

  10. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    Christine L. Howe

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  1. Jonine D. Figueroa
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Correspondence to Jonine D. Figueroa.

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Figueroa, J.D., Terry, M.B., Gammon, M.D. et al. Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression. Cancer Causes Control 20, 361–368 (2009). https://doi.org/10.1007/s10552-008-9250-6

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