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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 2 مورد

Familial gastric cancer syndromes: Associated genetic changes and indications for genetic testing

Familial gastric cancer syndromes: Associated genetic changes and indications for genetic testing
  Heritable genetic changes Clinical criteria for genetic testing Genetic testing
DGLBC syndrome, previously called HDGC syndrome Heterozygous germline pathogenic variant in CDH1 or CTNNA1 (autosomal dominant)

One or more of the following criteria, with cancer diagnoses confirmed on histology:

Family criteria (first- or second-degree blood relatives):

  • Two or more gastric cancer cases in kindred (regardless of age) with at least one confirmed diffuse gastric cancer
  • One or more cases of diffuse gastric cancer at any age, and one or more cases of lobular breast cancer at age <70 years, in different relatives
  • Two or more cases of lobular breast cancer in relatives <50 years of age

Individual criteria:

  • Diffuse gastric cancer in an individual under the age of 50
  • Diffuse gastric cancer at any age in Maori individuals
  • Diffuse gastric cancer at any age in an individual with a personal or family history (first-degree relative) of cleft lip/palate
  • Personal history of both diffuse gastric cancer and lobular breast cancer, both diagnosed under the age of 70
  • Bilateral lobular breast cancer diagnosed at age <70
  • Gastric in situ signet ring cells or pagetoid spread of signet ring cells on a gastric biopsy in individuals <50 years of age
  • Sequencing of CDH1*
  • Individuals who are negative for a CDH1 pathogenic or likely pathogenic variant should be evaluated with sequencing of CTNNA1*
GAPPS Heterozygous germline pathogenic variant in the promotor 1B region of APC (autosomal dominant) One or more of the following criteria, with cancer diagnoses confirmed on histology:
  • Gastric polyps restricted to the body and fundus of the stomach with no evidence of colorectal or duodenal polyposis
  • More than 100 polyps carpeting the proximal stomach in the index case or more than 30 polyps in a first-degree relative
  • Mainly fundic gastric polyps, some with regions of dysplasia (or a relative with either dysplastic fundic gastric polyps or gastric adenocarcinoma)
  • Exclusions include other heritable gastric polyposis syndromes and use of a proton pump inhibitor
  • APC sequence analysis of the promoter region is not routinely performed and must be requested
Familial intestinal gastric cancer Causative gene variants have yet to be identified One or more of the following criteria, with cancer diagnoses confirmed on histology:
  • Two or more cases of gastric cancer in first-degree or second-degree relatives, with at least one confirmed case of intestinal histology in individuals <50 years
  • Three or more confirmed cases of intestinal gastric cancer in first-degree or second-degree relatives, independent of age
  • No established genetic testing; consider enrollment in a clinical trial
Refer to UpToDate for details of heritable (genetic) gastric cancer syndromes. Other genetic cancer syndromes may also carry an increased risk of gastric cancer. Acquired risk factors may also contribute, including Helicobacter pylori infection, alcohol intake, diet (foods preserved with salt, certain other cooking processes, types of foods), obesity, GERD, and social determinants of health.

CLIA: Clinical Laboratory Improvement Amendments; DGLBC: diffuse gastric and lobular breast cancer; GAPPS: gastric adenocarcinoma and proximal polyposis of the stomach; GERD: gastroesophageal reflux disease; HDGC: hereditary diffuse gastric cancer.

* All sequencing for clinical management should be done in a CLIA-certified laboratory (or an equivalent certification in other countries).

¶ Proton pump inhibitors can induce a proximal polyposis of the stomach that may mimic a gastric adenocarcinoma. Patients taking these drugs should undergo a repeat endoscopy off-therapy to confirm the diagnosis of gastric adenocarcinoma versus proximal polyposis of the stomach.

Adapted from:
  1. Olivieria C, Pinhiero H, Figueiredo J, et al. Familial gastric cancer: Genetic susceptibility, pathology, and implications for management. Lancet Oncol 2015; 16:e60.
  2. Blair V, McLeod M, Carneiro F, et al. Hereditary diffuse gastric cancer: Updated clinical practice guidelines. Lancet Oncology 2020; 21:e386.
  3. Li J, Woods S, Healey S, et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet 2016; 98:830.
  4. Genetics of Gastric Cancer (PDQ)–Health Professional Version. National Cancer Institute. https://www.cancer.gov/types/stomach/hp/gastric-genetics-pdq (Accessed on January 7, 2025).
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