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Hereditary diffuse gastric cancer(HDGC)

MedGen UID:
310839
Concept ID:
C1708349
Neoplastic Process
Synonyms: HDGC
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Hereditary diffuse carcinoma of stomach (716859000); Hereditary diffuse gastric cancer (716859000)
 
Genes (locations): CDH1 (16q22.1); IL1B (2q14.1); IL1RN (2q14.1); KRAS (12p12.1)
OMIM®: 137215
Orphanet: ORPHA26106

Definition

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant susceptibility for diffuse gastric cancer, a poorly differentiated adenocarcinoma that infiltrates into the stomach wall causing thickening of the wall (linitis plastica) without forming a distinct mass. Diffuse gastric cancer is also referred to as signet ring carcinoma or isolated cell-type carcinoma. The average age of onset of HDGC is 38 years, with a range of 14-69 years. The majority of the cancers in individuals with a CDH1 pathogenic variant occur before age 40 years. The estimated cumulative risk of gastric cancer by age 80 years is 80% for both men and women. Women also have a 39%-52% risk for lobular breast cancer. [from GTR]

Additional descriptions

From GeneReviews
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant susceptibility for diffuse gastric cancer, a poorly differentiated adenocarcinoma that infiltrates into the stomach wall causing thickening of the wall (linitis plastica) without forming a distinct mass. Diffuse gastric cancer is also referred to as signet ring carcinoma or isolated cell-type carcinoma. The average age of onset of HDGC is 38 years, with a range of 14-69 years. The majority of the cancers in individuals with a CDH1 pathogenic variant occur before age 40 years. The estimated cumulative risk of gastric cancer by age 80 years is 80% for both men and women. Women also have a 39%-52% risk for lobular breast cancer.  https://www.ncbi.nlm.nih.gov/books/NBK1139
From OMIM
Hereditary diffuse gastric cancer is an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. Identification of mutation carriers is important, because the characteristic microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is often not readily detectable by routine upper endoscopy screening (summary by Fitzgerald et al., 2010). HDGC is considered to be a distinct disease entity from the more common sporadic occurrence of gastric cancer (613659), which can be associated with environmental factors, such as Helicobacter pylori infection, high-fat diet, or smoking, and is often associated with somatic mutations in disease tissue.  http://www.omim.org/entry/137215
From GHR
Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.  https://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer

Clinical features

Stomach cancer
MedGen UID:
147066
Concept ID:
C0699791
Neoplastic Process
A cancer arising in any part of the stomach.
Chronic atrophic gastritis
MedGen UID:
42157
Concept ID:
C0017154
Disease or Syndrome
A form of chronic gastritis associated with atrophic gastric mucous membrane.
Stomach cancer
MedGen UID:
147066
Concept ID:
C0699791
Neoplastic Process
A cancer arising in any part of the stomach.
Cleft secondary palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Cleft upper lip
MedGen UID:
892653
Concept ID:
C4020893
A gap in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary diffuse gastric cancer

Professional guidelines

PubMed

Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology.
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee.
Genet Med 2015 Jan;17(1):70-87. Epub 2014 Nov 13 doi: 10.1038/gim.2014.147. PMID: 25394175
Kluijt I, Sijmons RH, Hoogerbrugge N, Plukker JT, de Jong D, van Krieken JH, van Hillegersberg R, Ligtenberg M, Bleiker E, Cats A; Dutch Working Group on Hereditary Gastric Cancer.
Fam Cancer 2012 Sep;11(3):363-9. doi: 10.1007/s10689-012-9521-y. PMID: 22388873
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.
J Med Genet 2010 Jul;47(7):436-44. doi: 10.1136/jmg.2009.074237. PMID: 20591882Free PMC Article
Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K; American Society of Clinical Oncology.
J Clin Oncol 2010 Feb 10;28(5):893-901. Epub 2010 Jan 11 doi: 10.1200/JCO.2009.27.0660. PMID: 20065170
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CA Cancer J Clin 2007 Mar-Apr;57(2):75-89. PMID: 17392385

Recent clinical studies

Etiology

Rogers M
Clin J Oncol Nurs 2016 Aug 1;20(4):443-5. doi: 10.1188/16.CJON.443-445. PMID: 27441520
Hallowell N, Badger S, Richardson S, Caldas C, Hardwick RH, Fitzgerald RC, Lawton J
Fam Cancer 2016 Oct;15(4):665-76. doi: 10.1007/s10689-016-9910-8. PMID: 27256430
van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ
Gastroenterology 2015 Oct;149(4):897-906.e19. Epub 2015 Jun 11 doi: 10.1053/j.gastro.2015.06.003. PMID: 26072394
Pinheiro H, Oliveira C, Seruca R, Carneiro F
Best Pract Res Clin Gastroenterol 2014 Dec;28(6):1055-68. Epub 2014 Sep 28 doi: 10.1016/j.bpg.2014.09.007. PMID: 25439071
Li J, McBean E, Li X, Berho M, Szomstein S, Rosenthal RJ
Surg Laparosc Endosc Percutan Tech 2013 Jun;23(3):e124-6. doi: 10.1097/SLE.0b013e3182773e38. PMID: 23752020

Diagnosis

Rogers M
Clin J Oncol Nurs 2016 Aug 1;20(4):443-5. doi: 10.1188/16.CJON.443-445. PMID: 27441520
Gurzu S, Jung I, Orlowska J, Sugimura H, Kadar Z, Turdean S, Bara T Jr
Pathol Res Pract 2015 Sep;211(9):629-32. Epub 2015 Jun 11 doi: 10.1016/j.prp.2015.06.003. PMID: 26150395
van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ
Gastroenterology 2015 Oct;149(4):897-906.e19. Epub 2015 Jun 11 doi: 10.1053/j.gastro.2015.06.003. PMID: 26072394
Li J, McBean E, Li X, Berho M, Szomstein S, Rosenthal RJ
Surg Laparosc Endosc Percutan Tech 2013 Jun;23(3):e124-6. doi: 10.1097/SLE.0b013e3182773e38. PMID: 23752020
Ottenhof NA, de Wilde RF, Morsink FH, de Leng WW, Ausems MG, Morreau H, van Hillegersberg R, Offerhaus GJ, Milne AN
Hum Pathol 2012 Mar;43(3):457-61. Epub 2011 Oct 10 doi: 10.1016/j.humpath.2011.06.008. PMID: 21992816

Therapy

Molinaro V, Pensotti V, Marabelli M, Feroce I, Barile M, Pozzi S, Laghi L, Serrano D, Bernard L, Bonanni B, Ranzani GN
Genes Chromosomes Cancer 2014 May;53(5):432-45. Epub 2014 Feb 3 doi: 10.1002/gcc.22155. PMID: 24493355
Lim YC, di Pietro M, O'Donovan M, Richardson S, Debiram I, Dwerryhouse S, Hardwick RH, Tischkowitz M, Caldas C, Ragunath K, Fitzgerald RC
Gastrointest Endosc 2014 Jul;80(1):78-87. Epub 2014 Jan 25 doi: 10.1016/j.gie.2013.11.040. PMID: 24472763
Bardram L, Hansen TV, Gerdes AM, Timshel S, Friis-Hansen L, Federspiel B
Fam Cancer 2014 Jun;13(2):231-42. doi: 10.1007/s10689-013-9698-8. PMID: 24389957
Francis WP, Rodrigues DM, Perez NE, Lonardo F, Weaver D, Webber JD
JSLS 2007 Jan-Mar;11(1):142-7. PMID: 17651578Free PMC Article
Norton JA, Ham CM, Van Dam J, Jeffrey RB, Longacre TA, Huntsman DG, Chun N, Kurian AW, Ford JM
Ann Surg 2007 Jun;245(6):873-9. doi: 10.1097/01.sla.0000254370.29893.e4. PMID: 17522512Free PMC Article

Prognosis

van der Post RS, Gullo I, Oliveira C, Tang LH, Grabsch HI, O'Donovan M, Fitzgerald RC, van Krieken H, Carneiro F
Adv Exp Med Biol 2016;908:371-91. doi: 10.1007/978-3-319-41388-4_18. PMID: 27573781
Hallowell N, Badger S, Richardson S, Caldas C, Hardwick RH, Fitzgerald RC, Lawton J
Fam Cancer 2016 Oct;15(4):665-76. doi: 10.1007/s10689-016-9910-8. PMID: 27256430
van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ
Gastroenterology 2015 Oct;149(4):897-906.e19. Epub 2015 Jun 11 doi: 10.1053/j.gastro.2015.06.003. PMID: 26072394
Li J, McBean E, Li X, Berho M, Szomstein S, Rosenthal RJ
Surg Laparosc Endosc Percutan Tech 2013 Jun;23(3):e124-6. doi: 10.1097/SLE.0b013e3182773e38. PMID: 23752020
Ottenhof NA, de Wilde RF, Morsink FH, de Leng WW, Ausems MG, Morreau H, van Hillegersberg R, Offerhaus GJ, Milne AN
Hum Pathol 2012 Mar;43(3):457-61. Epub 2011 Oct 10 doi: 10.1016/j.humpath.2011.06.008. PMID: 21992816

Clinical prediction guides

DA Silva Oliveira KC, Bona AB, DA Silva FJ, Pinheiro TM, DI Felipe Avila Alcantara D, Lamarao LM, Moreira-Nunes CA, Assumpcao PP, Burbano RR, Calcagno DQ
Anticancer Res 2017 May;37(5):2401-2406. doi: 10.21873/anticanres.11579. PMID: 28476807
van der Post RS, Gullo I, Oliveira C, Tang LH, Grabsch HI, O'Donovan M, Fitzgerald RC, van Krieken H, Carneiro F
Adv Exp Med Biol 2016;908:371-91. doi: 10.1007/978-3-319-41388-4_18. PMID: 27573781
Gurzu S, Jung I, Orlowska J, Sugimura H, Kadar Z, Turdean S, Bara T Jr
Pathol Res Pract 2015 Sep;211(9):629-32. Epub 2015 Jun 11 doi: 10.1016/j.prp.2015.06.003. PMID: 26150395
van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ
Gastroenterology 2015 Oct;149(4):897-906.e19. Epub 2015 Jun 11 doi: 10.1053/j.gastro.2015.06.003. PMID: 26072394
Humar B, Guilford P
Cancer Sci 2009 Jul;100(7):1151-7. Epub 2009 Apr 21 doi: 10.1111/j.1349-7006.2009.01163.x. PMID: 19432899

Recent systematic reviews

Sandoval JA, Fernandez-Pineda I, Malkan AD
J Pediatr Surg 2016 Apr;51(4):675-87. Epub 2016 Feb 3 doi: 10.1016/j.jpedsurg.2016.01.004. PMID: 26898681
Kluijt I, Sijmons RH, Hoogerbrugge N, Plukker JT, de Jong D, van Krieken JH, van Hillegersberg R, Ligtenberg M, Bleiker E, Cats A; Dutch Working Group on Hereditary Gastric Cancer.
Fam Cancer 2012 Sep;11(3):363-9. doi: 10.1007/s10689-012-9521-y. PMID: 22388873
Seevaratnam R, Coburn N, Cardoso R, Dixon M, Bocicariu A, Helyer L
Gastric Cancer 2012 Sep;15 Suppl 1:S153-63. Epub 2011 Dec 10 doi: 10.1007/s10120-011-0116-3. PMID: 22160243
Mastoraki A, Danias N, Arkadopoulos N, Sakorafas G, Vasiliou P, Smyrniotis V
Surg Oncol 2011 Dec;20(4):e223-6. Epub 2011 Aug 26 doi: 10.1016/j.suronc.2011.08.001. PMID: 21872467
Corso G, Pedrazzani C, Pinheiro H, Fernandes E, Marrelli D, Rinnovati A, Pascale V, Seruca R, Oliveira C, Roviello F
Eur J Cancer 2011 Mar;47(4):631-9. Epub 2010 Nov 22 doi: 10.1016/j.ejca.2010.10.011. PMID: 21106365

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