Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania

dc.contributor.authorRweyemamu, Linus Paul
dc.contributor.authorGültaşlar, Busra K
dc.contributor.authorAkan, Gokce
dc.contributor.authorDharsee, Nazma
dc.contributor.authorNamkinga, Lucy
dc.contributor.authorLyantagaye, Sylvester L
dc.contributor.authorYazici, Hulya
dc.contributor.authorAtalar, Fatmahan
dc.date.accessioned2022-11-24T12:51:33Z
dc.date.available2022-11-24T12:51:33Z
dc.date.issued2022-07-19
dc.descriptionN/Aen_US
dc.description.abstractBackground Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. Methods One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). Conclusions Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.en_US
dc.description.sponsorshipMinistry of Education, Science and Technology; University of Dar es Salaam through grant no. MCHAS-20131en_US
dc.identifier.citationRweyemamu LP, Gültaşlar BK, Akan G, Dharsee N, Namkinga LA, Lyantagaye SL, Yazici H and Fatmahan Atalar. Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania. Cancer Medicine. 2022;00:1-15. https://doi.org/10.1002/cam4.5091en_US
dc.identifier.doihttps://doi.org/10.1002/cam4.5091
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5909
dc.language.isoen_USen_US
dc.publisherWILEYen_US
dc.relation.ispartofseries2022;cam4.5091
dc.relation.ispartofseries;cam4.5091
dc.subjectBreast cancer, BRCA1/2, germline variants, next-generation sequencing, Tanzania.en_US
dc.subjectBreast cancer, BRCA1/2, germline variants, next-generation sequencing, Tanzania.en_US
dc.titleBreast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzaniaen_US
dc.typeJournal Article, Peer Revieweden_US
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