Study of CDH1 germline mutation in hereditary diffuse gastric cancer and lobular breast cancer: a multicenter study in Iran
-
Marveh Rahmati
,
Elmira Ebrahimi
,
Reza Shirkoohi
,
Habibollah Mahmoodzadeh
,
Ahad Mohammanjad
,
Hedyeh Malekisarvar
,
Zahra Valizadeh
,
Marzieh Dehghani
,
Shirin Haghighat
,
Maryam Marzban
,
Kazem Zendehdel
Abstract
Introduction: Mutations occurring in the CDH1 gene elevate the susceptibility to the development of hereditary diffuse gastric cancer (HDGC) as well as lobular breast cancer (LBC). LBCs with CDH1 germline mutations are classified as hereditary breast cancers, devoid of any indication of gastric carcinoma. As prophylactic gastrectomy is a recommended course of treatment for individuals with CDH1 mutations, it is advised that genetic testing be conducted for those who meet the criteria established by the National Comprehensive Cancer Network (NCCN). This study aimed to screen patients with HDGC for CDH1 testing and clinical management for the prevention of HDGC. Moreover, patients with LBC are tested for CDH1 mutation. Materials and Methods: In this multicenter study, thirty-one patients with HDGC were selected among 615 patients and admitted for CDH1 mutation testing. PCR for all 16 exons of CDH1 and Sanger sequencing were performed. Patients with LBC who are negative for BRCA1/2 were also included in this study regardless of gastric cancer history. Results: The results showed that 5.04% of patients with DGC were identified as HDGC of which 9.6% of individuals had a pathogenic CDH1 mutation and only 15.38% of cases with a family history carried germline mutation in CDH1. Furthermore, 7.6% of patients with LBC and negative for a family history of gastric cancer have CDH1 mutation. Discussion: All patients who met the NCCN criteria were not CDH1 mutation-positive, indicating other genes should be involved in DGC. Moreover, patients with LBC and negative for BRCA1/2 are recommended for testing the mutation in CDH1.
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14. Schrader KA, Masciari S, Boyd N, Wiyrick S, Kaurah P, Senz J, et al. Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam Cancer [Internet]. 2008;7:73–82. Available from: http://link.springer.com/10.1007/s10689-007-9172-6
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18. Moridnia A, Kheirollahi M, Tabatabaeifar MA, Zeinalian M. Comparative study on mutations in CDH1 gene in Iranian patients with hereditary diffuse gastric cancer (HDGC) and sporadic diffuse gastric cancer (SDGC). J Isfahan Med Sch. 2017;35.
19. Kheirollahi M, Saneipour M, Tabatabaiefar MA, Zeinalian M, Minakari M, Moridnia A. New variants in the cdh1 gene in iranian families with hereditary diffuse gastric cancer. Middle East J Cancer. 2020;11.
20. Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007;297.
21. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, et al. Somatic mutations and deletions of the e-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol. 2013;31.
22. Muslim OT, Abdulmaged MA, Radhi AA. The distribution of gastric malignancies in al-diwaniyah province-iraq, a retrospective study. Int J Res Pharm Sci. 2019;10.
23. Onitilo AA, Aryal G, Engel JM. Hereditary diffuse gastric cancer: A family diagnosis and treatment. Clin Med Res. 2013;11.
24. Lobo S, Benusiglio PR, Coulet F, Boussemart L, Golmard L, Spier I, et al. Cancer predisposition and germline CTNNA1 variants. Eur J Med Genet [Internet]. 2021;64:104316. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1769721221001828
25. Corso G, Veronesi P, Sacchini V, Galimberti V. Prognosis and outcome in CDH1-mutant lobular breast cancer. Eur. J. Cancer Prev. 2018.
26. Mirandola S, Pellini F, Granuzzo E, Lorenzi M, Accordini B, Ulgelmo M, et al. Multidisciplinary management of CDH1 germinal mutation and prophylactic management hereditary lobular breast cancer: A case report. Int J Surg Case Rep. 2019;58.
2. Dehdari T, Dehdari L, Jazayeri S. Diet-related stomach cancer behavior among iranian college students: A text messaging intervention. Asian Pacific J Cancer Prev. 2016;17.
3. Ekström AM, Serafini M, Nyrén O, Hansson L-E, Ye W, Wolk A. Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: A population-based case-control study in Sweden. Int J Cancer [Internet]. 2000;87:133–40. Available from: https://onlinelibrary.wiley.com/doi/10.1002/1097-0215(20000701)87:1%3C133::AID-IJC20%3E3.0.CO;2-E
4. Pinheiro H, Oliveira C, Seruca R, Carneiro F. Hereditary diffuse gastric cancer – Pathophysiology and clinical management. Best Pract Res Clin Gastroenterol [Internet]. 2014;28:1055–68. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1521691814001504
5. Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 2015;1.
6. Cosma L-S, Schlosser S, Tews HC, Müller M, Kandulski A. Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches. Int J Mol Sci [Internet]. 2022;23:7821. Available from: https://www.mdpi.com/1422-0067/23/14/7821
7. Lowstuter K, Espenschied CR, Sturgeon D, Ricker C, Karam R, LaDuca H, et al. Unexpected CDH1 Mutations Identified on Multigene Panels Pose Clinical Management Challenges. JCO Precis Oncol [Internet]. 2017;1–12. Available from: https://ascopubs.org/doi/10.1200/PO.16.00021
8. Oliveira C, Ferreira P, Nabais S, Campos L, Ferreira A, Cirnes L, et al. E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients. Eur J Cancer [Internet]. 2004;40:1897–903. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0959804904003673
9. Chen Y, Kingham K, Ford JM, Rosing J, Van Dam J, Jeffrey RB, et al. A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer. Ann Surg Oncol. 2011;
10. Lewis FR, Mellinger JD, Hayashi A, Lorelli D, Monaghan KG, Carneiro F, et al. Prophylactic total gastrectomy for familial gastric cancer. Surgery. 2001;
11. Petrovchich I, Ford JM. Genetic predisposition to gastric cancer. Semin. Oncol. 2016.
12. Lim YC, Di Pietro M, O’Donovan M, Richardson S, Debiram I, Dwerryhouse S, et al. Prospective cohort study assessing outcomes of patients from families fulfilling criteria for hereditary diffuse gastric cancer undergoing endoscopic surveillance. Gastrointest Endosc. 2014;
13. Corso G, Intra M, Trentin C, Veronesi P, Galimberti V. CDH1 germline mutations and hereditary lobular breast cancer. Fam Cancer [Internet]. 2016;15:215–9. Available from: http://link.springer.com/10.1007/s10689-016-9869-5
14. Schrader KA, Masciari S, Boyd N, Wiyrick S, Kaurah P, Senz J, et al. Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam Cancer [Internet]. 2008;7:73–82. Available from: http://link.springer.com/10.1007/s10689-007-9172-6
15. Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology. JNCCN J. Natl. Compr. Cancer Netw. 2016.
16. van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, et al. Hereditary diffuse gastric cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J. Med. Genet. 2015.
17. Benusiglio PR, Malka D, Rouleau E, Pauw A De, Buecher B, Noguès C, et al. CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: A multicentre study. J Med Genet. 2013;50.
18. Moridnia A, Kheirollahi M, Tabatabaeifar MA, Zeinalian M. Comparative study on mutations in CDH1 gene in Iranian patients with hereditary diffuse gastric cancer (HDGC) and sporadic diffuse gastric cancer (SDGC). J Isfahan Med Sch. 2017;35.
19. Kheirollahi M, Saneipour M, Tabatabaiefar MA, Zeinalian M, Minakari M, Moridnia A. New variants in the cdh1 gene in iranian families with hereditary diffuse gastric cancer. Middle East J Cancer. 2020;11.
20. Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007;297.
21. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, et al. Somatic mutations and deletions of the e-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol. 2013;31.
22. Muslim OT, Abdulmaged MA, Radhi AA. The distribution of gastric malignancies in al-diwaniyah province-iraq, a retrospective study. Int J Res Pharm Sci. 2019;10.
23. Onitilo AA, Aryal G, Engel JM. Hereditary diffuse gastric cancer: A family diagnosis and treatment. Clin Med Res. 2013;11.
24. Lobo S, Benusiglio PR, Coulet F, Boussemart L, Golmard L, Spier I, et al. Cancer predisposition and germline CTNNA1 variants. Eur J Med Genet [Internet]. 2021;64:104316. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1769721221001828
25. Corso G, Veronesi P, Sacchini V, Galimberti V. Prognosis and outcome in CDH1-mutant lobular breast cancer. Eur. J. Cancer Prev. 2018.
26. Mirandola S, Pellini F, Granuzzo E, Lorenzi M, Accordini B, Ulgelmo M, et al. Multidisciplinary management of CDH1 germinal mutation and prophylactic management hereditary lobular breast cancer: A case report. Int J Surg Case Rep. 2019;58.
| Files | ||
| Issue | Vol 15 No 2 (2023) | |
| Section | Original Articles | |
| Keywords | ||
| CDH1 mutation Hereditary Diffuse Gastric Cancer Lobular breast cancer Prophylactic gastrectomy | ||
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How to Cite
1.
Rahmati M, Ebrahimi E, Shirkoohi R, Mahmoodzadeh H, Mohammanjad A, Malekisarvar H, Valizadeh Z, Dehghani M, Haghighat S, Marzban M, Zendehdel K. Study of CDH1 germline mutation in hereditary diffuse gastric cancer and lobular breast cancer: a multicenter study in Iran. Basic Clin Cancer Res. 2024;15(2):130-139.
