Abstract
The etiology of breast cancer in Africa is scarcely investigated. Breast cancer was responsible for 456/2,233 cancer patients (20.4%) ascertained between 1999 and 2004 at Gezira University, Central Sudan. Male breast cancer accounted for 16/456 patients (3.5%), 275/440 female patients (62.5%) were premenopausal and 150/440 cases (34%) occurred in women with ≥5 childbirths. We characterized for germline BRCA1/2 mutations a one-year series of patients (34 females, 1 male) selected by diagnosis within age 40 years or male gender. Overall 33/35 patients were found to carry 60 BRCA1/2 variants, of which 17 (28%) were novel, 22 (37%) reported in populations from various geographic areas and 21 (35%) reported worldwide. Detected variants included 5 truncating mutations, one of which (in BRCA2) was in the male patient. The 55 non-truncating variants included 3 unclassified variants predicted to affect protein product and not co-occurring with a truncating mutation in the same gene. Patients were from different tribes but AMOVA showed that most BRCA1/2 variation was within individuals (86.41%) and patients clustered independently of tribe in a phylogenetic tree. Cluster analysis based on age at cancer diagnosis and reproductive variables split female patients in two clusters that, by factor analysis, were explained by low versus high scores of the total period occupied by pregnancies and lactation. The cluster with low scores comprised all 4 patients with truncating mutations and 3 of the 4 carriers of unclassified variants predicted to affect protein product. Our findings suggest that in Central Sudan BRCA1/2 represent an important etiological factor of breast cancer in males and young women less exposed to pregnancy and lactation. Factors other than BRCA1/2 may contribute to breast cancer in young highly multiparous women who breast-fed for prolonged periods.
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Acknowledgments
We thank the patients who took part in this research. Our study was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), the Italian Ministry of Education, University and Research (MIUR-COFIN project 2003 “Molecular epidemiology and analysis of tumor progression in familial breast-ovarian cancer”, coordinated by S. Venuta). Dr. Awadelkarim is the recipient of a Research Contract supported by the Faculty of Medicine, G. d’Annunzio University, Chieti. We thank the personnel of the Italian Embassy in Khartoum and of the Sudanese Embassy in Rome (in particular Mr. Saif Mahmoud) for their kind assistance. Collaboration between CeSI and INMO is within the framework of activities developed by CeSI as Special Consultant of ECOSOC of the United Nations.
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Khalid Dafaallah Awadelkarim and Gitana Aceto equally contributed to this work.
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Awadelkarim, K.D., Aceto, G., Veschi, S. et al. BRCA1 and BRCA2 status in a Central Sudanese series of breast cancer patients: interactions with genetic, ethnic and reproductive factors. Breast Cancer Res Treat 102, 189–199 (2007). https://doi.org/10.1007/s10549-006-9303-z
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DOI: https://doi.org/10.1007/s10549-006-9303-z