title: Concomitant loss of heterozygosity at the BRCA1 and FHIT genes as a prognostic factor in sporadic breast cancer.
abstract: Previous studies have shown loss of heterozygosity (LOH) at the BRCA1 and FHIT genes in sporadic primary breast cancer. The aim of this study was to evaluate concomitant LOH at the BRCA1 and FHIT genes in sporadic breast cancer and investigate its influence on patient survival. Loss of heterozygosity was determined using microsatellite markers. The analysis on the informative cases (n = 72) indicated LOH at both the BRCA1 and FHIT loci in 25 cases (35%), the absence of LOH at both loci in 23 cases (32%), and the presence of LOH at one of the loci in 24 cases (33%). The concomitant LOH was associated with poor prognostic factors, such as large tumors (P = 0.01), axillary nodal involvement (P < 0.01), histologic grade III (P < 0.01), vascular invasion (P = 0.01), and negative hormone receptor (P = 0.02). After a median follow-up period of 48 months, the concomitant LOH group had the shortest survival (P < 0.02 by log-rank test; P < 0.05 by Cox model; hazard ratio of 4.87), compared with patients without LOH. These data suggest that concomitant allelic losses of the BRCA1 and FHIT genes are associated with more aggressive breast tumors.
authors.affiliation: Department of Surgical Oncology, West Paraná Union to Study and Fight Cancer, Cascavel, Paraná, Brazil. ewss@ig.com.br
authors.forename: Emerson Wander
authors.initials: EW
authors.lastname: Silva Soares
authors.forename: Savana Camilo
authors.initials: SC
authors.lastname: de Lima Santos
authors.forename: Alexandre Galvão
authors.initials: AG
authors.lastname: Bueno
authors.forename: Iglenir João
authors.initials: IJ
authors.lastname: Cavalli
authors.forename: Luciane Regina
authors.initials: LR
authors.lastname: Cavalli
authors.forename: Jorge Eduardo
authors.initials: JE
authors.lastname: Fouto Matias
authors.forename: Enilze Maria
authors.initials: EM
authors.lastname: de Souza Fonseca Ribeiro
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase