Gastric cancer incidence overall has declined in the U.S. during the past 50 years but the incidence of adenocarcinoma of the gastric cardia and lower esophagus has recently substantially increased. Compared to gastric and esophageal cancer overall, adenocarcinoma of the gastric cardia and lower esophagus is characterized by a high male to female ratio and is relatively more common in whites. Experimental and clinical evidence suggest that duodenal gastric or esophageal reflux may play an etioloqic role in proximal gastric carcinogenesis. Histamine2 (H2)-receptor antagonists (H2-blockers) were introduced in the mid-1970s and have become the treatment of choice for peptic ulcer disease and gastroesophageal reflux disorders. H2 blockers are potentially involved in gastric carcinogenesis. These drugs alter gastric acid production, increasing gastric pH and allowing reflux of alkaline duodenal refluxate into the proximal stomach and lower esophagus. Furthermore these drugs can be nitrosated to form mutagenic N-nitroso compounds. We propose a population-based case-control study to evaluate the role of this category of drugs (including possible effects of age at first use, dose, duration of use, latency and condition for which H2- blockers were prescribed) as well as other possible risk factors (e.g., use of other categories of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, prior benign conditions of the stomach and esophagus, smoking and alcohol use, and dietary factors) in the etiology of adenocarcinoma of the gastric cardia/lower esophagus. Consecutively diagnosed cases will be identified by the population-based cancer registry in Los Angeles County over 4.5 years. Controls will be neighborhood controls matched 2:1 with cases on age, race, and sex. A total of 440 case-control triplets will be interviewed during the course of this study.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA059636-05
Application #
2390775
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Verma, Mukesh
Project Start
1993-06-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
2000-03-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Gharahkhani, Puya; Tung, Joyce; Hinds, David et al. (2016) Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus. Hum Mol Genet 25:828-35
Ek, Weronica E; Lagergren, Katarina; Cook, Michael et al. (2016) Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma. Int J Cancer 138:1146-52
Lagergren, Katarina; Ek, Weronica E; Levine, David et al. (2015) Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium. PLoS One 10:e0138738
Thrift, Aaron P; Shaheen, Nicholas J; Gammon, Marilie D et al. (2014) Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study. J Natl Cancer Inst 106:
Thrift, Aaron P; Risch, Harvey A; Onstad, Lynn et al. (2014) Risk of esophageal adenocarcinoma decreases with height, based on consortium analysis and confirmed by Mendelian randomization. Clin Gastroenterol Hepatol 12:1667-76.e1
Cook, Michael B; Corley, Douglas A; Murray, Liam J et al. (2014) Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS One 9:e103508
Jiang, Xuejuan; Tseng, Chiu-Chen; Bernstein, Leslie et al. (2014) Family history of cancer and gastroesophageal disorders and risk of esophageal and gastric adenocarcinomas: a case-control study. BMC Cancer 14:60
Levine, David M; Ek, Weronica E; Zhang, Rui et al. (2013) A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus. Nat Genet 45:1487-93
Ek, Weronica E; Levine, David M; D'Amato, Mauro et al. (2013) Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux. J Natl Cancer Inst 105:1711-8
Liao, Linda M; Vaughan, Thomas L; Corley, Douglas A et al. (2012) Nonsteroidal anti-inflammatory drug use reduces risk of adenocarcinomas of the esophagus and esophagogastric junction in a pooled analysis. Gastroenterology 142:442-452.e5; quiz e22-3

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