Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Familial Cancer
Published in: Familial Cancer 1/2019

Open Access 01-01-2019 | Original Article

Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori

Authors: Christopher Hakkaart, Lis Ellison-Loschmann, Robert Day, Andrew Sporle, Jonathan Koea, Pauline Harawira, Soo Cheng, Michelle Gray, Tracey Whaanga, Neil Pearce, Parry Guilford

Published in: Familial Cancer | Issue 1/2019

Login to get access

Abstract

New Zealand Māori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primarily characterised by an extreme lifetime risk of developing diffuse gastric cancer. Pathogenic CDH1 mutations are well described in Māori families in New Zealand. However, the contribution of these mutations to the high incidence of gastric cancer is unknown. We have used next-generation sequencing, Sanger sequencing, and Multiplex Ligation-dependent Probe Amplification to examine germline CDH1 in an unselected series of 94 Māori gastric cancer patients and 200 healthy matched controls. Overall, 18% of all cases, 34% of cases diagnosed with diffuse-type gastric cancer, and 67% of cases diagnosed aged less than 45 years carried pathogenic CDH1 mutations. After adjusting for the effect of screening known HDGC families, we estimate that 6% of all advanced gastric cancers and 13% of all advanced diffuse-type gastric cancers would carry germline CDH1 mutations. Our results demonstrate that germline CDH1 mutations are a significant contributor to the high frequency of diffuse gastric cancer in New Zealand Māori.
Appendix
Available only for authorised users
Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386CrossRef
2.
Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49CrossRefPubMed
3.
4.
Ministry of Social Development (2016) The social report 2016—Te pūrongo oranga tangata. Ministry of Social Development, Wellington
5.
Teng AM, Atkinson J, Disney G, Wilson N, Sarfati D, McLeod M, Blakely T (2016) Ethnic inequalities in cancer incidence and mortality: census-linked cohort studies with 87 million years of person-time follow-up. BMC Cancer 16(1):755CrossRefPubMedPubMedCentral
6.
Ministry of Health (2015) Cancer: new registrations and deaths 2012. Ministry of Health, Wellington
7.
Biggar M, Srinivasa S, Wickramarachchi B, Babor R, Poole GH, Hill AG (2011) Gastric cancer location and histological subtype in Pacific people and Māori defies international trends. J N Z Med Assoc 124:1331
8.
Blair V, Charlton A, Sutton T, Martin I (2003) High incidence of ‘diffuse type’sporadic gastric cancer in Maori New Zealanders: possible evidence of further cancer susceptibility in addition to the known truncating germline E-caderin mutations in Maori families with hereditary diffuse gastric cancer? Gastroenterology 124(4):A548CrossRef
9.
Guilford P, Hopkins J, Harraway J, McLeod M (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392(6674):402CrossRefPubMed
10.
van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KEC, Hardwick RH, Ausems MG (2015) Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 52(6):361–374CrossRefPubMed
11.
Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G (2015) Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol 1(1):23–32CrossRefPubMed
12.
Blair V, Martin I, Shaw D, Winship I, Kerr D, Arnold J, Harawira P, McLeod M, Parry S, Charlton A (2006) Hereditary diffuse gastric cancer: diagnosis and management. Clin Gastroenterol Hepatol 4(3):262–275CrossRefPubMed
13.
Ellison-Loschmann L, Sporle A, Corbin M, Cheng S, Harawira P, Gray M, Whaanga T, Guilford P, Koea J, Pearce N (2017) Risk of stomach cancer in Aotearoa/New Zealand: a Māori population based case-control study. PLoS ONE 12(7):e0181581CrossRefPubMedPubMedCentral
14.
15.
16.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20(9):1297–1303CrossRefPubMedPubMedCentral
17.
Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, Land SJ, Lu X, Ruden DM (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6(2):80–92CrossRefPubMedPubMedCentral
18.
Lek M, Karczewski K, Minikel E, Samocha K, Banks E, Fennell T, O’Donnell-Luria A, Ware J, Hill A, Cummings B (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536(7616):285CrossRefPubMedPubMedCentral
19.
Consortium GP (2010) A map of human genome variation from population scale sequencing. Nature 467(7319):1061CrossRef
20.
Tennessen JA, Bigham AW, O’Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G (2012) Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337(6090):64–69CrossRefPubMedPubMedCentral
21.
Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4(7):1073–1081CrossRefPubMed
22.
23.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249CrossRefPubMedPubMedCentral
24.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405CrossRefPubMedPubMedCentral
25.
26.
Team RC (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
27.
Molinaro V, Pensotti V, Marabelli M, Feroce I, Barile M, Pozzi S, Laghi L, Serrano D, Bernard L, Bonanni B (2014) Complementary molecular approaches reveal heterogeneous CDH1 germline defects in Italian patients with hereditary diffuse gastric cancer (HDGC) syndrome. Genes Chromosom Cancer 53(5):432–445CrossRefPubMed
28.
Masciari S, Larsson N, Senz J, Boyd N, Kaurah P, Kandel MJ, Harris LN, Pinheiro HC, Troussard A, Miron P (2007) Germline E-cadherin mutations in familial lobular breast cancer. J Med Genet 44(11):726–731CrossRefPubMedPubMedCentral
29.
Frebourg T, Oliveira C, Hochain P, Karam R, Manouvrier S, Graziadio C, Vekemans M, Hartmann A, Baert-Desurmont S, Alexandre C (2006) Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer. J Med Genet 43(2):138–142CrossRefPubMedPubMedCentral
30.
Vogelaar IP, Figueiredo J, van Rooij IA, Simões-Correia J, van der Post RS, Melo S, Seruca R, Carels CE, Ligtenberg MJ, Hoogerbrugge N (2012) Identification of germline mutations in the cancer predisposing gene CDH1 in patients with orofacial clefts. Hum Mol Genet 22(5):919–926CrossRefPubMed
31.
Hansford S, LiChang H, Kaurah P, Woo M, Shumansky K, Schaeffer DF, Corso G, Zogopoulos G, Gallinger S, Pinheiro H (2014) Genetic basis of hereditary gastric cancer: beyond the CDH1 locus. Can Res 74(19 Supplement):1282–1282
32.
Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, Suriano G, Zaor S, Van Manen L, Gilpin C (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297(21):2360–2372CrossRefPubMed
33.
Brooks-Wilson A, Kaurah P, Suriano G, Leach S, Senz J, Grehan N, Butterfield Y, Jeyes J, Schinas J, Bacani J (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41(7):508–517CrossRefPubMedPubMedCentral
34.
Levy-Lahad E, Catane R, Eisenberg S, Kaufman B, Hornreich G, Lishinsky E, Shohat M, Weber BL, Beller U, Lahad A (1997) Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet 60(5):1059PubMedPubMedCentral
35.
King M-C, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646CrossRefPubMed
36.
Warner E, Foulkes W, Goodwin P, Meschino W, Blondal J, Paterson C, Ozcelik H, Goss P, Allingham-Hawkins D, Hamel N (1999) Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91(14):1241–1247CrossRefPubMed
37.
Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, Smotkin D, Ben-David Y, Rosenblatt J, Russo D (2000) BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 66(4):1259–1272CrossRefPubMedPubMedCentral
38.
McLaughlin J, Dryer D, Logan H, Mao Y, Marrett L, Morrison H, Schacter B, Villeneuve G, Waters C, Semenciw R (2006) Canadian cancer statistics 2006. National Cancer Institute of Canada, Toronto
39.
da Silva Tatley F, Aldwell FE, Dunbier AK, Guilford PJ (2003) N-terminal E-cadherin peptides act as decoy receptors for Listeria monocytogenes. Infect Immun 71(3):1580–1583CrossRefPubMedPubMedCentral
40.
Hamon M, Bierne H, Cossart P (2006) Listeria monocytogenes: a multifaceted model. Nat Rev Microbiol 4(6):423–434CrossRefPubMed
41.
Pentecost M, Otto G, Theriot JA, Amieva MR (2006) Listeria monocytogenes invades the epithelial junctions at sites of cell extrusion. PLoS Pathog 2(1):e3CrossRefPubMedPubMedCentral
Metadata
Title
Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori
Authors
Christopher Hakkaart
Lis Ellison-Loschmann
Robert Day
Andrew Sporle
Jonathan Koea
Pauline Harawira
Soo Cheng
Michelle Gray
Tracey Whaanga
Neil Pearce
Parry Guilford
Publication date
01-01-2019
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2019
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-018-0080-8

Other articles of this Issue 1/2019

Familial Cancer 1/2019 Go to the issue

Original Article

Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes

Short Communication

Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma

Original Article

Sarcoma in neurofibromatosis 2: case report and review of the literature

Original Article

Hemangioblastoma in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: a phenotypic overlap between VHL and HLRCC Syndromes

Short Communication

Delineating a new feature of constitutional mismatch repair deficiency (CMMRD) syndrome: breast cancer

Short Communication

Identification of a novel GREM1 duplication in a patient with multiple colon polyps
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits