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Open Access 01-12-2022 | Breast Cancer | Research

Screening of BRCA1/2 variants in Mauritanian breast cancer patients

Authors: Selma Mohamed Brahim, Ekht Elbenina Zein, Crystel Bonnet, Cheikh Tijani Hamed, Malak Salame, Mohamed Vall Zein, Meriem Khyatti, Ahmedou Tolba, Ahmed Houmeida

Published in: BMC Cancer | Issue 1/2022

Abstract

Background and study aim

Carrying a pathogenic BRCA1/2 variant increases greatly young women’s risk of developing breast cancer (BC). This study aimed to provide the first genetic data on BC in Mauritania.

Methods

Using NGS based screening; we searched for BRCA1/2 variants in DNA samples from 137 patients diagnosed for hereditary BC.

Results

We identified 16 pathogenic or likely pathogenic (PV) variants carried by 38 patients. Two predominant BRCA1 PV variants were found: c.815_824dup and c.4986 + 6 T > C in 13 and 7 patients, respectively. Interestingly, three novels BRCA1/2 predicted pathogenic variants have also been detected. Notably, no specific distribution of BRCA1/2 variants was observed regarding triple negative breast cancer (TNBC) or patient gender status.

Conclusions

In this first genetic profiling of BC in Mauritania, we identified a substantial number of BRCA1/2 pathogenic variants. This finding could be important in the future diagnosis and prevention policy of hereditary BC in Mauritania.

Globocan 2020: New Global Cancer Data | UICC. Accessed 22 Mar. 2022. https://www.uicc.org/news/globocan-2020-new-global-cancer-data

Epidemiology of breast cancer - ScienceDirect. Accessed 31 Jan. 2022. https://www.sciencedirect.com/science/article/abs/pii/S0755498219304105?via%3Dihub

Catana A, Apostu AP, Antemie RG. Multi gene panel testing for hereditary breast cancer - is it ready to be used? Med Pharm Rep. Published online July 4, 2019. Doi: https://doi.org/10.15386/mpr-1083

Turashvili G and Brogi E. Tumor Heterogeneity in Breast Cancer Front. Med., December 08, 2017| https://doi.org/10.3389/fmed.2017.00227.

Rosenthal ET, Evans B, Kidd J, et al. Increased identification of candidates for high-risk breast Cancer screening through expanded genetic testing. J Am Coll Radiol. 2017;14(4):561–8. https://doi.org/10.1016/j.jacr.2016.10.003.CrossRefPubMed

Goidescu IG, Caracostea G, Eniu DT, Stamatian FV. Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population. Clujul Med 1957. 2018; 91(2):157–165. Doi: https://doi.org/10.15386/cjmed-894.

Bono M, Fanale D, Corsini LR, Brando C, Madonia G, et al. Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge. ESMO Open. 2021;6(4):100235. https://doi.org/10.1016/j.esmoop.2021.100235.CrossRefPubMedPubMedCentral

Fanale D, Incorvaia L, Filorizzo C, et al. Detection of germline mutations in a cohort of 139 patients with bilateral breast Cancer by multi-gene panel testing: impact of pathogenic variants in other genes beyond BRCA1/2. Cancers. 2020;12(9):E2415. https://doi.org/10.3390/cancers12092415.CrossRefPubMed

Fanale D, Bono M, Calò V, et al. BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype-phenotype correlation in a cohort of 531 patients. Ther Adv. Med Oncol. 2020;12:1758835920975326. https://doi.org/10.1177/1758835920975326.CrossRef

10.

Kamps R, Brandão RD, van den Bosch BJ, et al. Next-generation sequencing in oncology: genetic diagnosis, risk prediction and Cancer classification. Int J Mol Sci. 2017;18(2):308. https://doi.org/10.3390/ijms18020308.CrossRefPubMedCentral

11.

Vieira R, Biller G, Uemura G, Ruiz C, Curado M. Breast cancer screening in developing countries. Clinics. 2017; 72:244–253. doi:https://doi.org/10.6061/clinics/2017 (04)09,https://pubmed.ncbi.nlm.nih.gov/30130155/

12.

Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world Breast Cancer (Dove Medical Press), 11, 151–164. https://doi.org/10.2147/BCTT.S176070.

13.

Mouh FZ, Slaoui M, Razine R, El Mzibri M, Amrani M. Clinicopathological, treatment and event-free survival characteristics in a Moroccan population of triple-negative breast Cancer. Breast Cancer Basic Clin Res. 2020;14:117822342090642. https://doi.org/10.1177/1178223420906428.CrossRef

14.

Bhinder MA, Sadia H, Mahmood N, et al. Consanguinity: A blessing or menace at population level? Ann Hum Genet 2019;83(4):214–219. https://doi.org/10.1111/ahg.12308.

15.

Anwar WA, Khyatti M, Hemminki K. Consanguinity and genetic diseases in North Africa and immigrants to Europe. Eur J Pub Health. 2014;24(suppl 1):57–63. https://doi.org/10.1093/eurpub/cku104.CrossRef

16.

Mohamed Brahim S, Zein E, Houmeida A, Tolba A. General Oncology Care in Mauritania. In: Al-Shamsi HO, Abu-Gheida IH, Iqbal F, Al-Awadhi A, eds. Cancer in the Arab World. Springer; 2022:149–161. doi:https://doi.org/10.1007/978-981-16-7945-2_10.

17.

Zahedi R, Molavi Vardanjani H, Baneshi MR, et al. Incidence trend of breast Cancer in women of eastern Mediterranean region countries from 1998 to 2019: a systematic review and meta-analysis. BMC Womens Health 2020; 20(1):53. https://doi.org/10.1186/s12905-020-00903-z.

18.

Dobson R. Black women have a higher risk of breast cancer than white women. BMJ. 2008;336(7636):116. https://doi.org/10.1136/bmj.39461.648750.DB.CrossRefPubMedCentral

19.

Danforth DN. Disparities in breast cancer outcomes between Caucasian and African American women: a model for describing the relationship of biological and nonbiological factors. Breast Cancer Res BCR. 2013;15(3):208. https://doi.org/10.1186/bcr3429.CrossRefPubMed

20.

Fitzpatrick MB, Rendi MH, Kiviat NB, et al. Pathology of Senegalese breast cancers. Pan Afr Med J. 2019:34:67. https://doi.org/10.11604/pamj.2019.34.67.17993.

21.

Pace LE, Shulman LN. Breast Cancer in sub-Saharan Africa: challenges and opportunities to reduce mortality. Oncologist. 2016;21(6):739–44. https://doi.org/10.1634/theoncologist.2015-0429.CrossRefPubMedPubMedCentral

22.

Inequities in breast cancer treatment in sub-Saharan Africa: findings from a prospective multi-country observational study. Springermedizinde Accessed January 31, 2022. https://www.springermedizin.de/inequities-in-breast-cancer-treatment-in-sub-saharan-africa find/17064096.

23.

Laraqui A, Uhrhammer N, Lahlou-Amine I, et al. Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian Cancer in Moroccan population. Int J Med Sci. 2013;10(1):60–7. https://doi.org/10.7150/ijms.5014.CrossRefPubMed

24.

Boujemaa M, Hamdi Y, Mejri N, et al. Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia. Bandapalli OR, ed. PLOS ONE. 2021; 16(1):e0245362. https://doi.org/10.1371/journal.pone.0245362

25.

El Ansari FZ, Jouali F, Marchoudi N, et al. Screening of BRCA1/2 genes mutations and copy number variations in patients with high risk for hereditary breast and ovarian cancer syndrome (HBOC). BMC Cancer. 2020;20(1):747. https://doi.org/10.1186/s12885-020-07250-0.

26.

Laitman Y, Friebel TM, Yannoukakos D, et al. The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in middle eastern, north African, and south European countries. Hum Mutat. 2019;40(11):e1–e23. https://doi.org/10.1002/humu.23842.CrossRefPubMed

27.

Ndiaye R, Diop JPD, Bourdon-Huguenin V, et al. Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal. Npj. Genomic Med. 2020;5(1):1–6. https://doi.org/10.1038/s41525-020-0114-7.CrossRef

28.

Mefford HC, Baumbach L, Panguluri RC, et al. Evidence for a BRCA1 founder mutation in families of west African ancestry. Am J Hum Genet. 1999;65(2):575–8. https://doi.org/10.1086/302511.CrossRefPubMedPubMedCentral

29.

Walsh T, Casadei S et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci. 2011;108(44):18032–7. https://doi.org/10.1073/pnas.1115052108.

30.

Kour A, Sambyal V, Guleria K, et al. Screening of BRCA1 variants c.190T>C, 1307delT, g.5331G>a and c.2612C>T in breast cancer patients from North India. Genet Mol Biol. 2020;43(2):e20190014. https://doi.org/10.1590/1678-4685-gmb-2019-0014.CrossRefPubMedPubMedCentral

31.

Biancolella M, Ouédraogo NLM, Zongo N, et al. Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso. Hum Genomics. 2021;15(1):65. https://doi.org/10.1186/s40246-021-00365-w.

32.

Pal T, Bonner D, Cragun D et al. A high frequency of BRCA mutations in young black women with breast cancer residing in Florida. Cancer. 2015;121(23):4173–80. https://doi.org/10.1002/cncr.29645.CrossRefPubMed

33.

Rebbeck TR, Friebel TM, Friedman E, et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018;39(5):593–620. https://doi.org/10.1002/humu.23406.CrossRefPubMedPubMedCentral

34.

Chen X, Truong TTN, Weaver J, et al. Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression. Hum Mutat. 2006;27(5):427–35. https://doi.org/10.1002/humu.20319.CrossRefPubMed

35.

Vreeswijk MPG, Kraan JN, van der Klift HM, et al. Intronic variants in BRCA1 and BRCA2 that affect RNA splicing can be reliably selected by splice-site prediction programs. Hum Mutat. 2009;30(1):107–14. https://doi.org/10.1002/humu.20811.CrossRefPubMed

36.

Salmi F, Maachi F, Tazzite A, et al. Next-generation sequencing of BRCA1 and BRCA2 genes in Moroccan prostate cancer patients with positive family history. PLoS One. 2021;16(7):e0254101. https://doi.org/10.1371/journal.pone.0254101.CrossRefPubMedPubMedCentral

37.

Tian CQ, Darcy KM, Krivak TC, al. Assessment of the prognostic value of two common variants of BRCA1 and BRCA2 genes in ovarian Cancer patients treated with cisplatin and paclitaxel: a gynecologic oncology group study. Front. Oncol. 2013;3:206. https://doi.org/10.3389/fonc.2013.00206.CrossRef

38.

Rashid MU, Muhammad N, Amin A, Loya A, Hamann U. Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan. Breast Cancer Res Treat. 2017;161(2):191–201. https://doi.org/10.1007/s10549-016-4044-0.CrossRefPubMed

39.

Chen H, Wu J, Zhang Z, et al. Association between BRCA status and triple-negative breast Cancer: a Meta-analysis. Front Pharmacol. 2018;9:909. https://doi.org/10.3389/fphar.2018.00909.CrossRefPubMedPubMedCentral

40.

Incorvaia L, Fanale D, Bono M, et al. BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype-phenotype correlation in a cohort of 531 patients. Ther Adv. Med Oncol. 2020:12:1758835920975326. https://doi.org/10.1177/1758835920975326.

41.

Incorvaia L, Fanale D, Badalamenti G, et al. Hereditary breast and ovarian Cancer in families from southern Italy (Sicily)-prevalence and geographic distribution of pathogenic variants in BRCA1/2 genes. Cancers. 2020;12(5):E1158. https://doi.org/10.3390/cancers12051158.CrossRefPubMed

Title: Screening of BRCA1/2 variants in Mauritanian breast cancer patients
Authors: Selma Mohamed Brahim
Ekht Elbenina Zein
Crystel Bonnet
Cheikh Tijani Hamed
Malak Salame
Mohamed Vall Zein
Meriem Khyatti
Ahmedou Tolba
Ahmed Houmeida
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: BMC Cancer / Issue 1/2022
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-022-09903-8

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Abstract

Background and study aim

Methods

Results

Conclusions

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