Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

Summary: Background:
  Gastric cancers are cancers of the stomach. Hereditary ones are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. They want to learn about changes these cause in the body and about the genes involved.
  Objective:
  -To gather data about hereditary gastric cancer.
  Eligibility:
  -  People at least 2 years old with personal or family history with a hereditary gastric cancer.
  -  People at least 2 years old with gene changes that lead to such cancer or a lesion that may be hereditary.
  Design:
  -  Participants will be screened in a separate protocol.
  -  Participants will have:
  -  Physical exam
  -  Medical history
  -  Blood tests
  -  Scans
  -  Photos of skin lesions and other findings
  -  Gynecology consultation for women
  -  Cheek swab (some participants)
  -  For some participants, their relatives will be asked to join the study.
  -  Some participants will be asked to allow the study to get stored tissue samples for relatives who have died.
  -  Some samples will be sent to outside labs. All personal data will be protected. Samples will be destroyed when the study ends.
  -  Participants will get the results of genetic testing.
  -  Participants who cannot come to the NIH clinic may just give a cheek swab and have genetic testing done.
  -  Some participants will be contacted for more testing.

Detailed description: Background:
  -  An estimated 1-3% of gastric cancer cases occur within a familial background as part of an inherited cancer syndrome
  -  Hereditary Diffuse Gastric Cancer (HDGC) is the most frequent form of familial gastric cancer and has been linked to a germline mutation in the CDH1 gene
  -  Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a more recently described autosomal dominant syndrome characterized by fundic gland polyposis with antral sparing
  -  Other syndromes that predispose to gastric cancer include Li-Fraumeni syndrome, Lynch syndrome, Peutz-Jeghers syndrome, familial adenomatous polyposis syndrome and others
  Objectives:
  - Characterize the natural and clinical histories of hereditary gastric cancer syndromes
  Eligibility:
  - Individuals, and family members, who fulfill clinical criteria for a hereditary gastric cancer syndrome irrespective of previous genetic testing or treatment
  Design:
  -  These rare families will be recruited to genetically confirm diagnosis and study the natural history of hereditary gastric cancers
  -  Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.
  -  We will determine if there is a relationship between mutation and disease phenotype.

Eligibility: -INCLUSION CRITERIA:
  1. An individual, or their family members, with any of the following:
  -  Fulfills clinical criteria for Hereditary Diffuse Gastric Cancer (HGDC) syndrome or Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) syndrome
  -  Clinically suspicious personal or family medical history of gastric cancer or gastric cancer syndrome that warrants genetics evaluation
  -  Current diagnosis of gastric cancer and a germline mutation associated with a known cancer syndrome or an associated family history of gastric cancer
  -  Harbors a pathogenic germline mutation known to predispose to gastric cancer
  -  First-degree relatives, regardless of family history or personal history of cancer, with a documented deleterious germline mutation (including but not limited to LFS, FAP) known to predispose to gastric tumors
  -  Diagnosis or suspicion of a premalignant or malignant stomach lesion of suspected hereditary etiology
  2. Age > 18 years; patients under 18 years of age and greater than or equal to the age of 2 may participate if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood and urine collection does not add risk to the clinically indicated procedures.
  3. Ability of subject or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document.
  EXCLUSION CRITERIA:
  -N/A

Relevance to patient case: not relevant