Trial Information

Early Onset and Familial Gastric Cancer Registry

On a global basis, cancer of the stomach is the third most prevalent malignancy, with
947,000 expected new cases in 2000, and the second leading cancer cause of death (734,000
deaths annually). In the United States in 2003, approximately 22,400 cases of gastric cancer
will be diagnosed, and 12,100 patients will die from this disease1. The prognosis of this
disease is poor with 5-year relative survival rate of less than 20% for advanced disease.
The etiology of gastric cancer is attributable to both environmental and hereditary factors.
In the subset of patients with early onset disease and in particular among familial forms of
this disease, inherited susceptibility appears to play a dominant role. No single mutation
has been identified as responsible for early onset gastric cancer. Recent evidence has
emerged supporting the role of germline mutations in the E-cadherin gene (CDH1) as
conferring increased susceptibility to early onset diffuse type gastric cancer and better
understanding of other genes that predispose to gastric cancer tumorigenesis is anticipated
in the next several years2, 3. The primary purpose of this protocol is to establish a
prospective registry with detailed family history, gastric cancer risk factors, germline
DNA, and matched tumor and normal tissue for patients with early onset or familial gastric
cancer and their at-risk relatives. With this aim in mind, we have amended the registry to
include populations who are at low risk for germline etiology for the development of gastric
cancer. This includes a cohort of patients with gastric cancer who appear to have developed
the disease sporadically, as well as a cohort of control patients without gastric cancer.
Secondary objectives are 1) To measure the incidence of germline mutations in CDH1 among
"early onset" and "familial" gastric cancer patients and their relatives to determine the
importance of this variant in gastric cancer susceptibility and 2) To measure the prevalence
of abnormal gastric pathology among the cancer-free relatives of patients with "early onset"
and "familial" gastric cancer. In this research protocol, early onset gastric cancer (EOGC)
is defined as disease with age of onset before 50 that arises in the absence of family
history of gastric cancer or known hereditary cancer syndrome. Familial gastric cancer (FGC)
is defined as disease that occurs among individuals with at least one affected first degree
relative or two or more affected second degree relatives.Patients eligible for the
"sporadic" cohort are those not eligible for the EOGC or FGC. We will also establish a "low
risk" cohort for comparison. Patients eligible for the "low risk" cohort are those not
eligible for the EOGC or FGC. Study participants will fill out a questionnaire on their
family history and on their gastric cancer risk factors. Participants will be invited to
provide a sample of germline DNA for future genetic studies. Select high risk individuals,
for example those that meet criteria for Diffuse Hereditary Gastric Cancer(DHGC), will be
invited to participate in genetic counseling which is required prior to evaluation for CDH1
gene mutations. In addition, participants will be invited to provide tissue (tumor and
normal) where available, both fresh frozen and paraffin-embedded if possible. At risk
relatives of patients with EOGC/FGC will also be invited for a single upper endoscopy
screening test. At select sites, at risk relatives of patients with EOGC/FGC will also be
invited for a single upper endoscopy screening test. The Early Onset/Familial Gastric Cancer
Registry will serve as a source of clinical and pathological material that can be used to
identify future genetic abnormalities that may or may not predispose the development of
gastric cancer in these high-risk families and will help define a cohort for participation
in future chemoprevention/screening studies. Moreover, it will ensure that there is a
coherent unified approach for management of this rare group of patients.