title: BRCA1 and BRCA2 status in a Central Sudanese series of breast cancer patients: interactions with genetic, ethnic and reproductive factors.
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 > or =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.
authors.affiliation: Unit of Molecular Pathology and Genomics, Center for Sciences on the Ageing, Gabriele d'Annunzio University Foundation, Via Colle dell Ara, Chieti, Italy.
authors.forename: Khalid Dafaallah
authors.initials: KD
authors.lastname: Awadelkarim
authors.forename: Gitana
authors.initials: G
authors.lastname: Aceto
authors.forename: Serena
authors.initials: S
authors.lastname: Veschi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elhaj
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morgano
authors.forename: Ahmed Abdalla
authors.initials: AA
authors.lastname: Mohamedani
authors.forename: Elgaylani Abdalla
authors.initials: EA
authors.lastname: Eltayeb
authors.forename: Dafaallah
authors.initials: D
authors.lastname: Abuidris
authors.forename: Mario
authors.initials: M
authors.lastname: Di Gioacchino
authors.forename: Pasquale
authors.initials: P
authors.lastname: Battista
authors.forename: Fabio
authors.initials: F
authors.lastname: Verginelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cama
authors.forename: Nasr Eldin
authors.initials: NE
authors.lastname: Elwali
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000208:ethnology / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017584:Reproductive History; D018570:Risk Assessment; D013397:Sudan / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm