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

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.

Sex

All

Minimum age

2 Years

-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 CDH1, CTNNA1, SDH) known to predispose to gastric tumors.
   * Diagnosis or suspicion of a premalignant or malignant stomach lesion of suspected hereditary etiology.
2. Age \>= 2 years and older. Note: Patients under 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood, saliva or 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:

None.

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• BACKGROUNDvan der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15. PMID 25979631
• DERIVEDGallanis AF, Bowden C, Lopez R, Turner J, Fasaye GA, Perati SR, Hernandez JM, Blakely A, Davis JL. Reproductive decision-making and pregnancy in germline CDH1 variant carriers. J Med Genet. 2025 Sep 19;62(10):609-616. doi: 10.1136/jmg-2025-110857. PMID 40541392
• DERIVEDGallanis AF, Gamble LA, Samaranayake SG, Lopez R, Rhodes A, Rajasimhan S, Fasaye GA, Juma O, Connolly M, Joyce S, Berger A, Heller T, Blakely AM, Hernandez JM, Davis JL. Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy. J Clin Oncol. 2024 Feb 1;42(4):421-430. doi: 10.1200/JCO.23.01238. Epub 2023 Oct 30.