Official Title
Esophageal Cancer Genetics Studies
Brief Title
Esophageal Cancer Genetics Studies
Protocol ID
NCT00341276
Lead Sponsor
National Cancer Institute (NCI)
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.
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.
Several different but complementary approaches are proposed 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/nontumor study will be conducted in which a biological specimen bank consisting of
samples (tumor, nontumor, venous blood, finger stick blood, and buccal cells) from a
total of approximately 150 cases each 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. Comparative genomic hybridization and
microsatellite markers will be used to scan the genome in up to 20 cases to identify
potential hot spots followed by further testing of these hot spots and other candidate
markers in additional tumor/nontumor samples. 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 differences in polymorphisms for
selected genomic markers. Third, a casecontrol study will be conducted to evaluate hot
spots and candidate markers identified from the tumor/nontumor study and potential
gene-environment interactions. Finally, a linkage study will be conducted by identifying
and collecting information and DNA from cases and first degree relatives in special
highly informative families (those with 2 or more cases having obtainable DNA) as well as
population-based ascertainment and collection of information and DNA from all new cases
from Yangcheng County.
Study Period
-
Enrollment Count
7,705 participants
Eligibility 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.
Filters
Esophageal Cancer
Gastric (Cardia, Body) Cancer
COMPLETED
ADULT
OLDER_ADULT