During the past decade, the incidence of adenocarcinomas of the esophagus and gastric, cardia has increased markedly in the U.S., particularly among white men. In contrast, the rates of squamous cell carcinoma of the esophagus and other more distal stomach cancers have remained fairly stable. This proposal addresses possible reasons for the rising incidence of these tumors. Specifically, we propose to conduct a population-based case-control study of esophageal and gastric carcinomas (N=316) in men and women of all races who are between 30-74 years of age at the time of diagnosis, using the western Washington cancer registry. Controls (N=316) of similar age and gender from the same geographic area will be selected by random digit dialing. We will examine relative risks associated with: i) medications that inhibit gastric acid secretion, neutralize gastric acid, or irritate gastric/esophageal mucosa, ii) Barrett's esophagus and other benign gastrointestinal conditions, and iii) serologic evidence of prior infection with Helicobacter pylori. We also will collect information on other identified and hypothesized risk factors for cancers of the esophagus and stomach, including smoking, alcohol use, dietary intake, occupational history, and family history of gastrointestinal cancers. These and other exposures will be analyzed as independent predictors of risk in order to determine whether there are different risk factor profiles for adenocarcinomas of the esophagus/gastric cardia compared to other carcinomas of the esophagus and stomach, and as confounding variables in relation to the above specific aims. We will conduct in-person interviews, and obtain additional information from medical and pharmacy records. Cases and controls will be asked to provide a blood sample that will be used to measure antibodies to Helicobacter pylori, and for storage of leukocytes for future cytogenetic studies. Tumor tissue slides and blocks also will be obtained for all cases for uniform confirmation of histological diagnosis, determination of H. pylori infection status in tumor tissue, and future determination of specific oncogenes that may be associated with development of these adenocarcinomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA057949-02
Application #
3549921
Study Section
Special Emphasis Panel (SRC (56))
Project Start
1992-08-01
Project End
1995-07-31
Budget Start
1993-08-10
Budget End
1994-07-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Dong, Jing; Buas, Matthew F; Gharahkhani, Puya et al. (2018) Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants. Gastroenterology 154:1273-1281.e3
Buas, Matthew F; He, Qianchuan; Johnson, Lisa G et al. (2017) Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Gut 66:1739-1747
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Gharahkhani, Puya; Fitzgerald, Rebecca C; Vaughan, Thomas L et al. (2016) Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis. Lancet Oncol 17:1363-1373
Drahos, Jennifer; Xiao, Qian; Risch, Harvey A et al. (2016) Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium. Int J Cancer 138:55-64
Petrick, J L; Steck, S E; Bradshaw, P T et al. (2015) Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA). Br J Cancer 112:1291-300
Dai, James Y; de Dieu Tapsoba, Jean; Buas, Matthew F et al. (2015) A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus. Cancer Epidemiol Biomarkers Prev 24:1739-47
Lee, Eunjung; Stram, Daniel O; Ek, Weronica E et al. (2015) Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk. Cancer Epidemiol Biomarkers Prev 24:1801-3

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