Clinical trial NCT03030404: Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer
Official title: Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stomach Neoplasms
Stomach Cancer
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS)
Hereditary Diffuse Gastric Cancer (HDGC)
Familial Diffuse Gastric Cancer
Keywords: Genetics and Germline Mutations
Familial Background
Inherited Cancer Syndrome
Germline Mutation in the CDH1 Gene
Lobular Breast Cancer
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2017-01-25
Enrollment: 733
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

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.

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 germline mutations that predispose to gastric cancer such as SDH (succinate dehydrogenase protein subunits) gene and CTNNA1 (alpha catenin).

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 criteria: -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.

Primary outcomes:
measure: Characterization of the natural and clinical histories of hereditary gastric cancer syndromes
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Andrew M Blakely, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.