Contribution of BRCA1 and BRCA2 Germline Mutations to Early Onset Breast Cancer: a Series from North of Morocco

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2020 Sep 7

PMID 32894085

Citations 14

Authors

Joaira Bakkach

Mohamed Mansouri

Touria Derkaoui

Ali Loudiyi

Elmostafa El Fahime

Amina Barakat

Naima Ghailani Nourouti

Jaime Martinez de Villarreal

Carlos Cortijo Bringas

Mohcine Bennani Mechita

Affiliations

Soon will be listed here.

Abstract

Background: To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco.

Methods: Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform.

Results: Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer.

Conclusion: Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

Citing Articles

Frequency of somatic and germline variants of predisposition genes in young Chinese women with breast cancer.

Xu Y, Cai Q, Li J, Guo W, Chen L, Chen M Breast Cancer Res Treat. 2025; .

PMID: 39755988 DOI: 10.1007/s10549-024-07602-5.

Reproductive Risk Factor Patterns in Caribbean Women With Breast Cancer Across 4 Generations.

Sanchez-Covarrubias A, Chery M, Barreto-Coehlo P, Alexis C, Ali J, Diaz-Barbe A JAMA Netw Open. 2024; 7(10):e2438091.

PMID: 39378034 PMC: 11581535. DOI: 10.1001/jamanetworkopen.2024.38091.

Smartphone-based imaging colorimetric assay for monitoring the quality of curcumin in turmeric powder.

Jantra J, Teepoo S, Thananimit S Anal Sci. 2024; 40(7):1311-1321.

PMID: 38607598 DOI: 10.1007/s44211-024-00562-2.

A nomogram for predicting overall survival of breast cancer with regional lymph node metastasis in young women.

Sun R, Huang Y, Chen X, Jia H Transl Cancer Res. 2024; 13(2):542-557.

PMID: 38482426 PMC: 10928604. DOI: 10.21037/tcr-23-1825.

Frequency of germline pathogenic variants in breast cancer predisposition genes among young Turkish breast cancer patients.

Isiklar A, Aliyeva L, Yesilyurt A, Soyder A, Basaran G Breast Cancer Res Treat. 2023; 202(2):297-304.

PMID: 37615792 DOI: 10.1007/s10549-023-07074-z.

References

Martinez-Ferrandis J, Vega A, Chirivella I, Marin-Garcia P, Insa A, Lluch A . Mutational analysis of BRCA1 and BRCA2 in Mediterranean Spanish women with early-onset breast cancer: identification of three novel pathogenic mutations. Hum Mutat. 2003; 22(5):417-8. DOI: 10.1002/humu.9188. View

Belanger M, Dolman L, Arcand S, Shen Z, Chong G, Mes-Masson A . A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population. J Ovarian Res. 2015; 8:1. PMC: 4376165. DOI: 10.1186/s13048-015-0124-8. View

Papi L, Putignano A, Congregati C, Zanna I, Sera F, Morrone D . Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy. Breast Cancer Res Treat. 2008; 117(3):497-504. DOI: 10.1007/s10549-008-0190-3. View

Cini G, Mezzavilla M, Puppa L, Cupelli E, Fornasin A, DElia A . Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy. BMC Med Genet. 2016; 17:11. PMC: 4744627. DOI: 10.1186/s12881-016-0274-6. View

Koumpis C, Dimitrakakis C, Antsaklis A, Royer R, Zhang S, Narod S . Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece. Hered Cancer Clin Pract. 2011; 9:10. PMC: 3240809. DOI: 10.1186/1897-4287-9-10. View

Cavallone L, Arcand S, Maugard C, Nolet S, Gaboury L, Mes-Masson A . Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer. Fam Cancer. 2010; 9(4):507-17. DOI: 10.1007/s10689-010-9372-3. View

Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A . Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst. 2001; 93(16):1215-23. DOI: 10.1093/jnci/93.16.1215. View

Kim H, Cho D, Choi D, Choi S, Shin I, Park W . Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012; 134(3):1315-26. DOI: 10.1007/s10549-012-2159-5. View

Simard J, Dumont M, Moisan A, Gaborieau V, Malouin H, Durocher F . Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J Med Genet. 2006; 44(2):107-21. PMC: 2598057. DOI: 10.1136/jmg.2006.044388. View

10.

Tazzite A, Jouhadi H, Nadifi S, Aretini P, Falaschi E, Collavoli A . BRCA1 and BRCA2 germline mutations in Moroccan breast/ovarian cancer families: novel mutations and unclassified variants. Gynecol Oncol. 2012; 125(3):687-92. DOI: 10.1016/j.ygyno.2012.03.007. View

11.

Infante M, Duran M, Lasa A, Acedo A, de la Hoya M, Esteban-Cardenosa E . Two founder BRCA2 mutations predispose to breast cancer in young women. Breast Cancer Res Treat. 2009; 122(2):567-71. DOI: 10.1007/s10549-009-0661-1. View

12.

Uhrhammer N, Abdelouahab A, Lafarge L, Feillel V, Ben Dib A, Bignon Y . BRCA1 mutations in Algerian breast cancer patients: high frequency in young, sporadic cases. Int J Med Sci. 2008; 5(4):197-202. PMC: 2452980. DOI: 10.7150/ijms.5.197. View

13.

Caux-Moncoutier V, Castera L, Tirapo C, Michaux D, Remon M, Lauge A . EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. Hum Mutat. 2010; 32(3):325-34. DOI: 10.1002/humu.21414. View

14.

Pietschmann A, Mehdipour P, Atri M, Hofmann W, Hosseini-Asl S, Scherneck S . Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families. J Cancer Res Clin Oncol. 2005; 131(8):552-8. DOI: 10.1007/s00432-005-0678-8. View

15.

Novakovic S, Milatovic M, Cerkovnik P, Stegel V, Krajc M, Hocevar M . Novel BRCA1 and BRCA2 pathogenic mutations in Slovene hereditary breast and ovarian cancer families. Int J Oncol. 2012; 41(5):1619-27. PMC: 3583621. DOI: 10.3892/ijo.2012.1595. View

16.

Tonin P, Perret C, Lambert J, PARADIS A, Kantemiroff T, Benoit M . Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history. Int J Cancer. 2001; 95(3):189-93. DOI: 10.1002/1097-0215(20010520)95:3<189::aid-ijc1032>3.0.co;2-n. View

17.

Abdel-Razeq H, Al-Omari A, Zahran F, Arun B . Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan. BMC Cancer. 2018; 18(1):152. PMC: 5802063. DOI: 10.1186/s12885-018-4079-1. View

18.

Malone K, Daling J, Neal C, Suter N, OBrien C, Jonasdottir T . Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000; 88(6):1393-402. DOI: 10.1002/(sici)1097-0142(20000315)88:6<1393::aid-cncr17>3.0.co;2-p. View

19.

Goodwin P, Phillips K, West D, Ennis M, Hopper J, John E . Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study. J Clin Oncol. 2011; 30(1):19-26. DOI: 10.1200/JCO.2010.33.0068. View

20.

Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N . Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999; 91(11):943-9. DOI: 10.1093/jnci/91.11.943. View