National Cancer Institute Clinical and Laboratory Analysis of Familial Cancer

The purpose of this study is to continue the analysis begun on 09C0079 which was focused on identification of the genetic mutation associated with a new gastric polyposis syndrome, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS). GAPPS, first described in 2012, is an autosomal dominant gastric polyposis syndrome that confers a substantial risk for gastric adenocarcinoma. The GAPPS phenotype consists of a carpeting of greater than 100 fundic gland polyps (FGPs) in the oxyntic mucosa of the gastric body and fundus, with antral sparing with some FGPs displaying high-grade dysplasia. This is in contrast to sporadic FGPs that are benign, most often are not associated with high-grade dysplasia though low-grade dysplasia has been reported, and are fewer in number. Gastric FGPs have been found to be associated with Familial Adenomatous Polyposis (FAP) and attenuated FAP, which is an autosomal dominant condition associated with germ line mutations in APC which confers a phenotype consisting of multiple (>100) adenomatous polyps in the colon and rectum developing after the first decade of life. FGPs are reported to occur in 12-84% of patients with FAP, whereas sporadic FGPs are identified in ~5% of patients undergoing upper gastrointestinal endoscopy. Gastric adenocarcinoma arising from FGPs in individuals with FAP have been reported. Other manifestations of FAP and AFAP include polyps in the upper gastrointestinal tract, congenital hypertrophy of retinal pigment epithelium, osteomas and epidermoid cysts, supernumerary teeth, desmoid formation, and other malignancies such as thyroid, small bowel cancer, hepatoblastoma, and medulloblastoma. Thus far there are no reports in GAPPS of polyposis arising in the esophagus, gastric antrum, pylorus, small intestine, or colon.]]>
Inclusion Criteria Participants must meet one of the following criteria: Have been previously enrolled on the familial genetic analysis arm of NIH study 09-C-0079; OR, Be family members of patients previously enrolled on the familial genetic analysis arm 09-C-0079; Participants must be 18 years of age or older. Exclusion Criteria Inability to provide informed consent. ]]>
This protocol originated from The Natural History of Solid Organ Cancer Stem Cells (SOCSC), ClinicaTrials.gov: NCT00923052, PI, Itztak Avital, MD and then Udo Rudloff. MD, PhD. The protocol had a familial cancer family arm. Administratively, the familial cancer study arm and enrolled subjects moved to the Genetics Branch in the Center for Cancer Research, which was involved in the family collection and genomic analyses. This resulted in the change in Principal Investigator and new study title, Clinical and Laboratory Analysis of Familial Cancer. Familial genomic analyses were then completed on this protocol. All enrolled subjects signed the new study consent.]]>