The overall goal of this project is to understand the role of genetics in the etiology and prevention of upper gastrointestinal cancers (esophagus, gastric cardia, gastric body). The objective of current studies is to identify susceptibility genes for these cancers, beginning with cancer of the esophagus. BACKGROUND: Esophageal cancer is the 7th most common cause of cancer death worldwide. Several lines of evidence (family history, familial aggregation, segregation, cytogenetics) suggest that genetic factors may play an important role in the etiology of this malignancy. Identification of susceptibility genes may allow screening of populations to identify persons at particularly high risk who could then be targeted for prevention strategies (e.g., chemoprevention or early detection). METHODS: Several studies are in progress to study these cancers in persons from Shanxi Province, China, where rates are among the highest in the world, including collection of DNA for (1) a tumor/nontumor study of 450 cases, (2) a high-risk/low-risk population study of 200 subjects, (3) a case-control study of 1,400 cases and 1,400 controls, and (4) a linkage study in 150 families with multiple cases. PROGRESS: Tumor/nontumor DNA from over 400 cases has been collected. Initial genome-wide scans on 11 esophageal cancers identified 46 microsatellite markers with very frequent allelic loss (>75% of informative cases) representative of 18 regions, and these results have been confirmed in subsequent analysis of 46 additional cases. Probing with more dense microsatellite markers and/or candidate tumor suppressor genes has been conducted on chromosomes 9p, 13q, and 17p. Molecular progression studies have also been initiated to evaluate high frequency markers from LOH studies in precursor lesions. Case-control and linkage studies were initiated in late 1996 and continue to accrue subjects and families.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Prevention And Control (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CN000150-12
Application #
6433260
Study Section
(CPSB)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Cancer Prevention and Control
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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