title: Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population.
abstract: The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case-control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34-4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met-E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16-94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations.
authors.affiliation: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, P.O. Box 70061, Santiago, Chile. ljara@med.uchile.cl
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
authors.forename: Karen
authors.initials: K
authors.lastname: Dubois
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaete
authors.forename: Tomas
authors.initials: T
authors.lastname: de Mayo
authors.forename: Nikalai
authors.initials: N
authors.lastname: Ratkevicius
authors.forename: Teresa
authors.initials: T
authors.lastname: Bravo
authors.forename: Sonia
authors.initials: S
authors.lastname: Margarit
authors.forename: Rafael
authors.initials: R
authors.lastname: Blanco
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez
authors.forename: Enrique
authors.initials: E
authors.lastname: Waugh
authors.forename: Octavio
authors.initials: O
authors.lastname: Peralta
authors.forename: Jose M
authors.initials: JM
authors.lastname: Reyes
authors.forename: Gladys
authors.initials: G
authors.lastname: Ibáñez
authors.forename: Patricio
authors.initials: P
authors.lastname: González-Hormazábal
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D053903:DNA Breaks, Double-Stranded; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D013020:South America / Q000453:epidemiology
chemical_list: D004268:DNA-Binding Proteins; C112629:RAD51D protein, human; C110901:X-ray repair cross complementing protein 3