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

NCT03030404 | Completed

• 2 other identifiers: 17004317-C-0043
• Study Type: observational
• Target: 733
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stomach Neoplasms; Stomach Cancer; Hereditary Diffuse Gastric Cancer (HDGC); Familial Diffuse Gastric Cancer; Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS)

Keywords

Genetics and Germline Mutations; Familial Background; Inherited Cancer Syndrome; Germline Mutation in the CDH1 Gene; Lobular Breast Cancer; Natural History

Outcome Measures

Primary Outcomes (1)

• Characterization of the natural and clinical histories of hereditary gastric cancer syndromes

  Characterization of the natural and clinical histories of hereditary gastric cancer syndromes

  10 years

Study Arms (1)

Cohort 1

Subjects with suspicious personal or family medical history of gastric cancer or gastric cancer syndrome.

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals, and family members, who fulfill clinical criteria for a hereditary gastric cancer syndrome irrespective of previous genetic testing or treatment

You may qualify if:

• 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.
• 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.
• Ability of subject or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• None.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G, Santos TA, Claro I, Carvalho J, Nielsen C, Padilla S, Lum A, Talhouk A, Baker-Lange K, Richardson S, Lewis I, Lindor NM, Pennell E, MacMillan A, Fernandez B, Keller G, Lynch H, Shah SP, Guilford P, Gallinger S, Corso G, Roviello F, Caldas C, Oliveira C, Pharoah PD, Huntsman DG. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015 Apr;1(1):23-32. doi: 10.1001/jamaoncol.2014.168.

  PMID: 26182300 BACKGROUND

• Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C; International Gastric Cancer Linkage Consortium. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010 Jul;47(7):436-44. doi: 10.1136/jmg.2009.074237.

  PMID: 20591882 BACKGROUND

• van 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 BACKGROUND

• Gallanis 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 DERIVED

• Gallanis 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.

  PMID: 37903316 DERIVED

• Green BL, Gamble LA, Diggs LP, Nousome D, Patterson JC, Joughin BA, Gasmi B, Lux SC, Samaranayake SG, Miettinen M, Quezado M, Hernandez JM, Yaffe MB, Davis JL. Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis. Mol Cancer Res. 2023 Dec 1;21(12):1356-1365. doi: 10.1158/1541-7786.MCR-23-0122.

  PMID: 37707375 DERIVED

• Gamble LA, Lopez R, Rajasimhan S, Samaranayake SG, Bowden C, Famiglietti AL, Blakely AM, Jha S, Ahlman MA, Davis JL. Micronutrient Supplementation and Bone Health After Prophylactic Total Gastrectomy in Patients With CDH1 Variants. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2635-2642. doi: 10.1210/clinem/dgad137.

  PMID: 36950857 DERIVED

• Passi M, Gamble LA, Samaranayake SG, Schueler SA, Curtin BF, Fasaye GA, Bowden C, Gurram S, Quezado M, Miettinen M, Koh C, Heller T, Davis JL. Association of CDH1 Germline Variants and Colon Polyp Phenotypes in Patients with Hereditary Diffuse Gastric Cancer. Gastro Hep Adv. 2023;2(2):244-251. doi: 10.1016/j.gastha.2022.10.006. Epub 2022 Oct 28.

  PMID: 36776716 DERIVED

• Gamble LA, Grant RRC, Samaranayake SG, Fasaye GA, Koh C, Korman L, Asif B, Heller T, Hernandez JM, Blakely AM, Davis JL. Decision-making and regret in patients with germline CDH1 variants undergoing prophylactic total gastrectomy. J Med Genet. 2023 Mar;60(3):241-246. doi: 10.1136/jmg-2022-108733. Epub 2022 Jul 11.

  PMID: 35817563 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Stomach Neoplasms; Polyposis, Gastric; Neoplastic Syndromes, Hereditary

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Andrew M Blakely, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: January 25, 2017
• Study Start: January 27, 2017
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: May 29, 2026

Record last verified: 2026-03-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)