Esophageal Cancer Genetics Studies
Study Details
Study Description
Brief Summary
The overall goal of this project is to understand the role of genetics in the etiology and prevention of upper gastrointestinal cancer, primarily esophageal cancer, but also cancers of the gastric cardia and body.
Esophageal cancer is the second most common cause of cancer death in China and the seventh most common cause of cancer death worldwide. Evidence suggests that genetic factors may play an important role in the etiology of this malignancy, and identification of esophageal cancer 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). There are several lines of evidence supporting the idea that there is genetic susceptibility for esophageal cancer in high-risk Chinese populations, including an association of positive family history with increased risk, evidence of familial aggregation of cases, and segregation analyses suggesting Mendelian inheritance in high-risk families.
Several different but complementary approaches will be used to identify esophageal cancer susceptibility genes. (Because of etiologic similarities and for logistic reasons, parallel efforts will be made with gastric cardia and body cancers.) First, a tumor/non-tumor study will be conducted in which a biological specimen bank consisting of samples (tumor, non-tumor, venous blood, finger stick blood, and buccal cells) from several hundred cases of esophageal, gastric cardia, and gastric body cancers will be developed in Taiyuan that can be used for the identification of esophageal (as well as gastric cardia and body) cancer susceptibility genes and potential early genetic markers of these cancers. High-density genome-wide scans with microsatellite markers will be used in a limited number of cases to identify potential hot spots followed by further testing of these hot spots and other candidate markers in additional tumor/non-tumor samples. Premalignant morphologic lesions will also be examined. Second, blood samples for DNA will be collected from approximately 100 healthy individuals from high-risk (Yangcheng County) and low-risk (Beijing) areas to examine potential population differences in polymorphisms for selected genomic markers. Third, a large case-control study with cancers of the esophagus, cardia, and body of stomach will be conducted to evaluate polymorphisms in the candidate markers identified in other components of this project, and to evaluate gene-environment interactions. Finally, a family study will be conducted to evaluate linkage of candidate markers with cancer in families having 2 or more cases with cancers of the esophagus, cardia, and/or body of stomach.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
The overall goal of this project is to understand the role of genetics in the etiology and prevention of upper gastrointestinal cancer, primarily esophageal cancer, but also cancers of the gastric cardia and body.
Esophageal cancer is the fourth most common cause of cancer death in China and the seventh most common cause of cancer death worldwide. Evidence suggests that genetic factors may play an important role in the etiology of this malignancy, and identification of esophageal cancer 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). There are several lines of evidence supporting the idea that there is genetic susceptibility for esophageal cancer in high-risk Chinese populations, including an association of positive family history with increased risk, evidence of familial aggregation of cases, and segregation analyses suggesting Mendelian inheritance in high-risk families.
Five different but complementary approaches will be used to identify esophageal cancer susceptibility genes. (Because of etiologic similarities and for logistic reasons, parallel efforts will be made with gastric cardia and body cancers.) First, a tumor/non-tumor study will be conducted in which a biological specimen bank consisting of samples (tumor, non-tumor, venous blood, finger stick blood, and buccal cells) from several hundred cases of esophageal, gastric cardia, and gastric body cancers will be developed in Taiyuan that can be used for the identification of esophageal (as well as gastric cardia and body) cancer susceptibility genes and potential early genetic markers of these cancers. High-density genome-wide scans with microsatellite markers will be used in a limited number of cases to identify potential hot spots followed by further testing of these hot spots and other candidate markers in additional tumor/non-tumor samples. Premalignant morphologic lesions will also be examined. Second, blood samples for DNA will be collected from several hundred healthy individuals from high-risk (Yangcheng County) and low-risk (Beijing) areas to examine potential population differences in polymorphisms for selected genomic markers. Third, a large case-control study with cancers of the esophagus, cardia, and body of stomach will be conducted to evaluate polymorphisms in the candidate markers identified in other components of this project, and to evaluate gene-environment interactions. Fourth, a family study will be conducted to evaluate linkage of candidate markers with cancer in families having 2 or more cases with cancers of the esophagus, cardia, and/or body of stomach. Finally, an endoscopic study will be conducted to obtain specimens from a morphologic spectrum of disease ranging from normal to early invasive disease in order to characterize molecular progression.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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1 First, several hundred cases of esophageal cancer and gastric cancer (both cardia and body) ascertained in Taiyuan at the Shanxi Cancer Hospital. |
Outcome Measures
Primary Outcome Measures
- Esophageal cancer susceptibility (tumor /nontumor) [ongoing]
Obtain tumor and nontumor DNA samples from patients with esophageal cancer and examine markers in these tissues for differences that might suggest genomic loci associated with thedevelopment of (and, potentially, susceptibility to) esophageal cancer
- Gene frequency and associated risk (high risk / low risk) [ongoing]
Obtain DNA from healthy individuals from populations at high-risk and low-risk for esophageal cancer and examine their DNA for differences in gene frequency at selected loci
- Case-control [ongoing]
Obtain nontumor DNA from esophageal cancer cases and controls without cancer and examine candidate markers for differences that might be associated with esophageal cancer susceptibility
- Linkage of genetic markers [ongoing]
Obtain nontumor DNA from esophageal cancer cases and their family members and evaluate candidate markers for genetic linkage
Secondary Outcome Measures
- Gene environment interactions (case control) [ongoing]
Evaluate potential geneenvironment interactions in the etiology and prevention of esophageal cancer in the case-control study
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
All patients over the age of 18 presenting to the SCHI with upper GI signs or symptoms requiring upper GI endoscopy over a defined calendar period (depending on prevalence of premalignant lesions, but estimated to be approximately 3 years) will be potentially eligible for participation in this study.
Patients are eligible only if they meet one of the following two conditions: (1) a visible lesion unlikely to be cancer or (2) no visible lesions on routine endoscopy (without mucosal iodine staining) but an unstained (abnormal) lesion following iodine spraying.
Invitation for participation will be based solely on the visual appearance of an esophageal abnormality without or with mucosal iodine staining, but before histologic confirmation is obtained, and will occur during the same clinic visit as the qualifying endoscopic examination.
EXCLUSION CRITERIA:
Patients will not be invited to participate in this study until after they have undergone their routine endoscopic evaluation.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Shanxi Tumor Hospital and Institute | Taiyuan | China | ||
2 | Yangcheng County Cancer Hospital and Institute | Yangcheng | China |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Alisa M Goldstein, Ph.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
None provided.More Information
Publications
- Carter CL, Hu N, Wu M, Lin PZ, Murigande C, Bonney GE. Segregation analysis of esophageal cancer in 221 high-risk Chinese families. J Natl Cancer Inst. 1992 May 20;84(10):771-6.
- Guo W, Blot WJ, Li JY, Taylor PR, Liu BQ, Wang W, Wu YP, Zheng W, Dawsey SM, Li B, et al. A nested case-control study of oesophageal and stomach cancers in the Linxian nutrition intervention trial. Int J Epidemiol. 1994 Jun;23(3):444-50.
- Hu N, Dawsey SM, Wu M, Bonney GE, He LJ, Han XY, Fu M, Taylor PR. Familial aggregation of oesophageal cancer in Yangcheng County, Shanxi Province, China. Int J Epidemiol. 1992 Oct;21(5):877-82.
- 999995027
- OH95-C-N027
- NCT00558415
- NCT01338246