Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population
Date
2010
Type:
Article
item.page.extent
item.page.accessRights
item.contributor.advisor
ORCID:
Journal Title
Journal ISSN
Volume Title
Publisher
item.page.isbn
item.page.issn
item.page.issne
item.page.doiurl
item.page.other
item.page.references
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.
Description
item.page.coverage.spatial
item.page.sponsorship
Citation
La investigación del cáncer de mama y el tratamiento volumen 122 , paginas813–822 ( 2010
Keywords
Familial BC, XRCC3-Thr241Met, RAD51D-E233G, RAD51-135G[C, Polymorphism