Molecular characterization of early breast cancer onset to understand disease phenotypes in African patients.

Autor: Tonouo PD; Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon., Dina Bell E; Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.; Department of Medical Oncology Douala General Hospital, Douala, Cameroon., Tiofack Zebaze AA; Molecular Parasitology and Entomology Unit (MPEU), Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon., Ndounga E; Centre Hospitalier Universitaire de Brazzaville, Brazzaville, Congo., Noa Ananga S; Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.; Department of Medical Oncology Douala General Hospital, Douala, Cameroon., Atenguena E; Department of Medical Oncology, Yaoundé General Hospital Cameroon and the Cameroon Cancer Registry, Yaoundé, Cameroon., Simo G; Molecular Parasitology and Entomology Unit (MPEU), Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon., Njouendou AJ; Department of Biomedical Sciences, Faculty of Health Sciences, University of Buea, Buea, Cameroon., Lueong SS; Molecular Parasitology and Entomology Unit (MPEU), Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon. smiths-sengkwawoh.lueong@uk-essen.de.; Bridge Institute for Experimental Cancer Therapy, West German Cancer Center, University Hospital Essen, Hufeland Str. 55, 45147, Essen, Germany. smiths-sengkwawoh.lueong@uk-essen.de.; Division for Solid Tumor Translational Oncology, The German Consortium for Translational Cancer Research (DKTK) and the German Cancer Research Center (DKFZ), Essen/Düsseldorf Partner Site, West German Cancer Center, University Hospital Essen, Essen, Germany. smiths-sengkwawoh.lueong@uk-essen.de.
Jazyk: angličtina
Zdroj: Medical oncology (Northwood, London, England) [Med Oncol] 2022 Nov 09; Vol. 40 (1), pp. 13. Date of Electronic Publication: 2022 Nov 09.
DOI: 10.1007/s12032-022-01877-8
Abstrakt: Female breast cancer (BC) is the leading cause of cancer-related deaths worldwide with higher mortality rates and early onset in developing countries. The molecular basis of early disease onset is still elusive. We recruited 472 female breast cancer from two sub-Saharan African countries (Cameroon and Congo) between 2007 and 2018 and collected clinical data from these patients. To investigate the molecular drivers of early disease onset, we analyzed publicly available breast cancer molecular data from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) for copy number alteration, mutation and gene expression. Early BC onset (EOBRCA) (diagnosis before 45 years) was higher in African women compared with the TCGA cohort (51.7% vs 15.6%). The tumor grade, mitotic index, HER2 + phenotype, basal-like phenotype and ki67 were higher in EOBRCA for all cohorts. BC risk factors such as parity, breastfeeding early onset of menarche and use of hormonal contraceptives were significantly associated with EOBRCA (p < 0.05). EOBRCA was equally associated with copy number alterations in several oncogenes including CDH6 and FOXM1 and tumor suppressor including TGM3 and DMBT1 as well as higher TP53 mutation rates (OR: 2.93, p < 0.01). There was a significant enrichment of TGFß signaling in EOBRCA with TGM3 deletions, which was associated with high expression of all SMAD transcription factors as well as WNT ligands. The Frizzled receptors FZD1, FZD4 and FZD6 were significantly upregulated in EOBRCA, suggesting activation of non-canonical WNT signaling. Our data, suggest the implication of TGM3 deletion in early breast cancer onset. Further molecular investigations are warranted in African patients.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: