Trial Information

Esophageal Cancer Genetics Studies

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.