title: RAD51 135G>C polymorphism and risk of familial breast cancer in a South American population.
abstract: Several studies have reported that mutations in genes involved in maintenance of genome integrity may be responsible for increased cancer risk. Human RAD51, known to function in DNA repair, interacts with a number of proteins implicated in breast cancer (BC), including BRCA1 and BRCA2. Few studies have investigated the role of RAD51 gene variations in familial BC. To detect potential novel gene defects that may contribute to hereditary BC susceptibility, 143 patients belonging to 143 Chilean families tested for BRCA1 and BRCA2 mutations were screened for mutations in RAD51, using conformational sensitive gel electrophoresis (CSGE) and DNA sequencing. No mutations were detected in the exon or splice-boundary regions of the RAD51 gene in these families. The RAD51 135G>C polymorphism (c.-98G>C, rs1801320) was studied in a case-control design, to evaluate its possible association with BC susceptibility. The frequency of the RAD51 135C allele was established in 143 cases and 247 controls, using restriction fragment length polymorphism-polymerase chain reaction. RAD51 135C genotypes (G/C and C/C) were associated with an increased BC risk only among women with (a) a family history of BC, (b) BRCA1/2 negative (n = 131), and (c) age at onset <50 years (P = 0.020; OR = 2.17, 95% CI = 1.11-4.24). Thus, we propose that RAD51 135G>C polymorphism presents an increased risk of familial BC in women with age < 50 years at diagnosis, and this polymorphism may be a BC risk variant. This finding should be confirmed in other populations.
authors: 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: Lilian
authors: L
authors: Jara
authors: Monica L
authors: ML
authors: Acevedo
authors: Rafael
authors: R
authors: Blanco
authors: Victor G
authors: VG
authors: Castro
authors: Teresa
authors: T
authors: Bravo
authors: Fernando
authors: F
authors: Gómez
authors: Enrique
authors: E
authors: Waugh
authors: Octavio
authors: O
authors: Peralta
authors: Elsa
authors: E
authors: Cabrera
authors: José M
authors: JM
authors: Reyes
authors: Sandra
authors: S
authors: Ampuero
authors: Patricio
authors: P
authors: González-Hormazábal
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002677:Chile; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D051135:Rad51 Recombinase / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C495153:RAD51 protein, human; D051135:Rad51 Recombinase