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Hereditary diffuse gastric adenocarcinoma(HDGC)

MedGen UID:
310839
Concept ID:
C1708349
Neoplastic Process
Synonyms: HDGC; Hereditary diffuse gastric cancer
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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.
 
Gene (location): CDH1 (16q22.1)
 
Monarch Initiative: MONDO:0007648
OMIM®: 137215
Orphanet: ORPHA26106

Disease characteristics

Diffuse gastric and lobular breast cancer syndrome (DGLBCS) is associated with an increased risk, in males and females, of diffuse gastric cancer (DGC), a poorly differentiated adenocarcinoma (also referred to as signet ring cell carcinoma or isolated cell-type carcinoma) that infiltrates into the stomach wall, causing thickening of the wall (linitis plastica) without forming a distinct mass. In females with CDH1-related DGLBCS, but not in males, there is also an increased risk for lobular breast cancer (LBC), characterized by small, non-cohesive cells dispersed in the stroma or arranged in single-file infiltrating patterns. Cleft lip with or without cleft palate has also been reported in some individuals with CDH1-related DGLBCS. [from GeneReviews]
Authors:
Rita Barbosa-Matos  |  Lilian Córdova  |  Kasmintan Schrader, et. al.   view full author information

Additional descriptions

From OMIM
Diffuse gastric cancer and lobular breast cancer syndrome (DGLBC) 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). DGLBC 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 MedlinePlus Genetics
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://medlineplus.gov/genetics/condition/hereditary-diffuse-gastric-cancer

Clinical features

From HPO
Atrophic gastritis
MedGen UID:
42157
Concept ID:
C0017154
Disease or Syndrome
Atrophic gastritis (AG) is a histopathological entity that is characterized by chronic inflammation of the gastric mucosa with loss of gastric glandular cells and replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue.
Gastric cancer
MedGen UID:
44264
Concept ID:
C0024623
Neoplastic Process
In a review article on the genetic predisposition to gastric cancer, Bevan and Houlston (1999) concluded that several genes may be associated with an increased risk of gastric cancer. Gastric cancer is a manifestation of a number of inherited cancer predisposition syndromes, including hereditary nonpolyposis colon cancer (HNPCC1; see 120435), familial adenomatous polyposis (FAP; 175100), Peutz-Jeghers syndrome (PJS; 175200), Cowden disease (CD; 158350), the Li-Fraumeni syndrome (151623), and diffuse gastric and lobular breast cancer syndrome (DGLBC; 137215). Canedo et al. (2007) provided a review of genetic susceptibility to gastric cancer in patients infected with Helicobacter pylori (see 600263).
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Cleft 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).

Term Hierarchy

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

Professional guidelines

PubMed

Jacobson BC, Bhatt A, Greer KB, Lee LS, Park WG, Sauer BG, Shami VM
Am J Gastroenterol 2023 Jan 1;118(1):46-58. Epub 2022 Sep 6 doi: 10.14309/ajg.0000000000002100. PMID: 36602835
Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, Vogel A, Smyth EC; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org
Ann Oncol 2022 Oct;33(10):1005-1020. Epub 2022 Jul 29 doi: 10.1016/j.annonc.2022.07.004. PMID: 35914639
Xia JY, Aadam AA
J Surg Oncol 2022 Jun;125(7):1104-1109. doi: 10.1002/jso.26844. PMID: 35481909Free PMC Article

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Gastric Cancer, 2023

Suggested Reading

Recent clinical studies

Etiology

Röcken C
J Cancer Res Clin Oncol 2023 Jan;149(1):467-481. Epub 2022 Oct 19 doi: 10.1007/s00432-022-04408-0. PMID: 36260159Free PMC Article
López MJ, Carbajal J, Alfaro AL, Saravia LG, Zanabria D, Araujo JM, Quispe L, Zevallos A, Buleje JL, Cho CE, Sarmiento M, Pinto JA, Fajardo W
Crit Rev Oncol Hematol 2023 Jan;181:103841. Epub 2022 Oct 11 doi: 10.1016/j.critrevonc.2022.103841. PMID: 36240980
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F
Lancet 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5. PMID: 32861308
Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R
Int J Mol Sci 2020 Jun 4;21(11) doi: 10.3390/ijms21114012. PMID: 32512697Free PMC Article
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F
Cancer Epidemiol Biomarkers Prev 2014 May;23(5):700-13. Epub 2014 Mar 11 doi: 10.1158/1055-9965.EPI-13-1057. PMID: 24618998Free PMC Article

Diagnosis

López Sala P, Leturia Etxeberria M, Inchausti Iguíñiz E, Astiazaran Rodríguez A, Aguirre Oteiza MI, Zubizarreta Etxaniz M
Radiologia (Engl Ed) 2023 Jan-Feb;65(1):66-80. doi: 10.1016/j.rxeng.2022.10.011. PMID: 36842787
Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, Vogel A, Smyth EC; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org
Ann Oncol 2022 Oct;33(10):1005-1020. Epub 2022 Jul 29 doi: 10.1016/j.annonc.2022.07.004. PMID: 35914639
Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, Farjah F, Gerdes H, Gibson MK, Hochwald S, Hofstetter WL, Ilson DH, Keswani RN, Kim S, Kleinberg LR, Klempner SJ, Lacy J, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Outlaw D, Park H, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian N, Pluchino LA
J Natl Compr Canc Netw 2022 Feb;20(2):167-192. doi: 10.6004/jnccn.2022.0008. PMID: 35130500
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F
Lancet 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5. PMID: 32861308
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F
Cancer Epidemiol Biomarkers Prev 2014 May;23(5):700-13. Epub 2014 Mar 11 doi: 10.1158/1055-9965.EPI-13-1057. PMID: 24618998Free PMC Article

Therapy

Wang G, Huang Y, Zhou L, Yang H, Lin H, Zhou S, Tan Z, Qian J
Crit Rev Oncol Hematol 2024 Jun;198:104197. Epub 2023 Nov 10 doi: 10.1016/j.critrevonc.2023.104197. PMID: 37951282
Janjigian YY, Van Cutsem E, Muro K, Wainberg Z, Al-Batran SE, Hyung WJ, Molena D, Marcovitz M, Ruscica D, Robbins SH, Negro A, Tabernero J
Future Oncol 2022 Jun;18(20):2465-2473. Epub 2022 May 10 doi: 10.2217/fon-2022-0093. PMID: 35535555
Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Özgüroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA
JAMA Oncol 2021 Jun 1;7(6):895-902. doi: 10.1001/jamaoncol.2021.0275. PMID: 33792646Free PMC Article
Sexton RE, Al Hallak MN, Diab M, Azmi AS
Cancer Metastasis Rev 2020 Dec;39(4):1179-1203. Epub 2020 Sep 7 doi: 10.1007/s10555-020-09925-3. PMID: 32894370Free PMC Article
Ford AC, Yuan Y, Moayyedi P
Gut 2020 Dec;69(12):2113-2121. Epub 2020 Mar 23 doi: 10.1136/gutjnl-2020-320839. PMID: 32205420

Prognosis

Yang WJ, Zhao HP, Yu Y, Wang JH, Guo L, Liu JY, Pu J, Lv J
World J Gastroenterol 2023 Apr 28;29(16):2452-2468. doi: 10.3748/wjg.v29.i16.2452. PMID: 37179585Free PMC Article
Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, Limarzi F, Ferro J, Parente P, Fassan M
Pathologica 2020 Sep;112(3):166-185. doi: 10.32074/1591-951X-166. PMID: 33179620Free PMC Article
Pietrantonio F, Miceli R, Raimondi A, Kim YW, Kang WK, Langley RE, Choi YY, Kim KM, Nankivell MG, Morano F, Wotherspoon A, Valeri N, Kook MC, An JY, Grabsch HI, Fucà G, Noh SH, Sohn TS, Kim S, Di Bartolomeo M, Cunningham D, Lee J, Cheong JH, Smyth EC
J Clin Oncol 2019 Dec 10;37(35):3392-3400. Epub 2019 Sep 12 doi: 10.1200/JCO.19.01124. PMID: 31513484
Patel SH, Kooby DA
Surg Clin North Am 2011 Oct;91(5):1039-77. doi: 10.1016/j.suc.2011.06.009. PMID: 21889029
Brenner H, Rothenbacher D, Arndt V
Methods Mol Biol 2009;472:467-77. doi: 10.1007/978-1-60327-492-0_23. PMID: 19107449

Clinical prediction guides

Carneiro F
Best Pract Res Clin Gastroenterol 2022 Jun-Aug;58-59:101800. Epub 2022 May 4 doi: 10.1016/j.bpg.2022.101800. PMID: 35988963
Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, Limarzi F, Ferro J, Parente P, Fassan M
Pathologica 2020 Sep;112(3):166-185. doi: 10.32074/1591-951X-166. PMID: 33179620Free PMC Article
Ren N, Liang B, Li Y
Biosci Rep 2020 Oct 30;40(10) doi: 10.1042/BSR20200980. PMID: 33015704Free PMC Article
Digklia A, Wagner AD
World J Gastroenterol 2016 Feb 28;22(8):2403-14. doi: 10.3748/wjg.v22.i8.2403. PMID: 26937129Free PMC Article
Pasechnikov V, Chukov S, Fedorov E, Kikuste I, Leja M
World J Gastroenterol 2014 Oct 14;20(38):13842-62. doi: 10.3748/wjg.v20.i38.13842. PMID: 25320521Free PMC Article

Recent systematic reviews

Chen YC, Malfertheiner P, Yu HT, Kuo CL, Chang YY, Meng FT, Wu YX, Hsiao JL, Chen MJ, Lin KP, Wu CY, Lin JT, O'Morain C, Megraud F, Lee WC, El-Omar EM, Wu MS, Liou JM
Gastroenterology 2024 Apr;166(4):605-619. Epub 2024 Jan 2 doi: 10.1053/j.gastro.2023.12.022. PMID: 38176660
Wu X, Chen L, Cheng J, Qian J, Fang Z, Wu J
Nutrients 2022 Oct 12;14(20) doi: 10.3390/nu14204260. PMID: 36296944Free PMC Article
Ford AC, Yuan Y, Moayyedi P
Gut 2020 Dec;69(12):2113-2121. Epub 2020 Mar 23 doi: 10.1136/gutjnl-2020-320839. PMID: 32205420
Yusefi AR, Bagheri Lankarani K, Bastani P, Radinmanesh M, Kavosi Z
Asian Pac J Cancer Prev 2018 Mar 27;19(3):591-603. doi: 10.22034/APJCP.2018.19.3.591. PMID: 29579788Free PMC Article
Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, Graham DY
Gastroenterology 2016 May;150(5):1113-1124.e5. Epub 2016 Feb 2 doi: 10.1053/j.gastro.2016.01.028. PMID: 26836587

Supplemental Content

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    Curated

    • NCCN, 2023
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Gastric Cancer, 2023

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