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Hereditary diffuse gastric cancer(HDGC)

MedGen UID:
310839
Concept ID:
C1708349
Neoplastic Process
Synonyms: GASTRIC CANCER, FAMILIAL DIFFUSE; HDGC
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
 
Genes (locations): CDH1 (16q22.1); IL1B (2q14.1); IL1RN (2q14.1); KRAS (12p12.1)
OMIM®: 137215

Disease characteristics

Excerpted from the GeneReview: Hereditary Diffuse Gastric Cancer
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 GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Pardeep Kaurah  |  David G Huntsman   view full author information

Additional descriptions

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.  http://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer

Clinical features

Stomach cancer
MedGen UID:
506674
Concept ID:
CN167852
Finding
A cancer arising in any part of the stomach.
Cleft palate
MedGen UID:
504379
Concept ID:
CN000170
Finding
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:
504391
Concept ID:
CN000197
Finding
A gap in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Chronic atrophic gastritis
MedGen UID:
505279
Concept ID:
CN002344
Finding
A form of chronic gastritis associated with atrophic gastric mucous membrane.
Stomach cancer
MedGen UID:
506674
Concept ID:
CN167852
Finding
A cancer arising in any part of the stomach.

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. [Epub ahead of print] PMID: 25645574
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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 20065170
Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, Morris E, Pisano E, Schnall M, Sener S, Smith RA, Warner E, Yaffe M, Andrews KS, Russell CA; American Cancer Society Breast Cancer Advisory Group
CA Cancer J Clin 2007 Mar-Apr;57(2):75-89. PMID: 17392385

Recent clinical studies

Etiology

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. [Epub ahead of print] PMID: 25439071
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. [Epub ahead of print] 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
Yamada M, Fukagawa T, Nakajima T, Asada K, Sekine S, Yamashita S, Okochi-Takada E, Taniguchi H, Kushima R, Oda I, Saito Y, Ushijima T, Katai H
Gastric Cancer 2014 Oct;17(4):750-6. Epub 2013 Sep 15 doi: 10.1007/s10120-013-0298-y. [Epub ahead of print] PMID: 24037103
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

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. [Epub ahead of print] PMID: 24493355
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
Oliveira C, Seruca R, Hoogerbrugge N, Ligtenberg M, Carneiro F
Eur J Hum Genet 2013 Aug;21(8) Epub 2013 Feb 27 doi: 10.1038/ejhg.2012.247. [Epub ahead of print] PMID: 23443028Free PMC Article
Onitilo AA, Aryal G, Engel JM
Clin Med Res 2013 Feb;11(1):36-41. Epub 2012 Jun 21 doi: 10.3121/cmr.2012.1071. [Epub ahead of print] PMID: 22723466Free PMC Article
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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] 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
Schuetz JM, Leach S, Kaurah P, Jeyes J, Butterfield Y, Huntsman D, Brooks-Wilson AR
Cancer Epidemiol Biomarkers Prev 2012 Dec;21(12):2272-4. Epub 2012 Oct 15 doi: 10.1158/1055-9965.EPI-12-1110. [Epub ahead of print] PMID: 23071139
Humar B, Toro T, Graziano F, Müller H, Dobbie Z, Kwang-Yang H, Eng C, Hampel H, Gilbert D, Winship I, Parry S, Ward R, Findlay M, Christian A, Tucker M, Tucker K, Merriman T, Guilford P
Hum Mutat 2002 May;19(5):518-25. doi: 10.1002/humu.10067. PMID: 11968084

Prognosis

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. [Epub ahead of print] 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
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
Kim S, Chung JW, Jeong TD, Park YS, Lee JH, Ahn JY, Kim do H, Choi KD, Lee W, Song HJ, Lee GH, Chun S, Jung HY, Min WK, Kim JH
Fam Cancer 2013 Sep;12(3):503-7. doi: 10.1007/s10689-012-9595-6. PMID: 23264079
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. [Epub ahead of print] PMID: 21992816

Clinical prediction guides

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. [Epub ahead of print] 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
Schuetz JM, Leach S, Kaurah P, Jeyes J, Butterfield Y, Huntsman D, Brooks-Wilson AR
Cancer Epidemiol Biomarkers Prev 2012 Dec;21(12):2272-4. Epub 2012 Oct 15 doi: 10.1158/1055-9965.EPI-12-1110. [Epub ahead of print] PMID: 23071139
Simões-Correia J, Figueiredo J, Lopes R, Stricher F, Oliveira C, Serrano L, Seruca R
PLoS One 2012;7(3):e33783. Epub 2012 Mar 21 doi: 10.1371/journal.pone.0033783. PMID: 22470475Free PMC Article
Matsukuma KE, Mullins FM, Dietz L, Zehnder JL, Ford JM, Chun NM, Schrijver I
Hum Pathol 2010 Aug;41(8):1200-3. doi: 10.1016/j.humpath.2010.01.022. PMID: 20624523

Recent systematic reviews

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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 21106365
Sharma RR, London MJ, Magenta LL, Posner MC, Roggin KK
J Gastrointest Surg 2009 Oct;13(10):1874-87. Epub 2009 Jun 10 doi: 10.1007/s11605-009-0935-2. [Epub ahead of print] PMID: 19513795

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