title: Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population.
abstract: Inability to correctly repair DNA damage is known to play a role in the development of breast cancer. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been identified, which modify the DNA repair capacity, which in turn may affect the risk of developing breast cancer. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 62 SNPs in 29 genes in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. Five SNPs were associated with breast cancer. SNPs rs13312840 and rs769416 in the NBS1 gene were associated with a decrease in breast cancer risk (OR TT vs. TC/CC = 0.58; 95% CI, 0.37-0.92; P = 0.019 and OR GG vs. GT/TT = 0.23, 95% CI 0.06-0.85, P = 0.017, respectively). The variant allele of MRE11A rs556477 was also associated with a reduced risk of developing the disease (OR AA vs. AG/GG = 0.76; 95% CI, 0.64-0.91; P = 0.0022). MUS81 rs545500 and PBOV1 rs6927706 SNPs were associated with an increased risk of developing breast cancer (OR GG vs. GC/CC = 1.21, 95% CI, 1.02-1.45; P = 0.031; OR AA vs. AG/GG = 1.53, 95% CI, 1.07-2.18; P = 0.019, respectively). Finally, haplotype-based tests identified significant associations between specific haplotypes in MRE11A and NBS1 genes and breast cancer risk. Further large-scale studies are needed to confirm these results.
authors.affiliation: Department of Electron Microscope/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Loizidou
authors.forename: Marios A
authors.initials: MA
authors.lastname: Cariolou
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Robert F
authors.initials: RF
authors.lastname: Newbold
authors.forename: Evy
authors.initials: E
authors.lastname: Bashiardes
authors.forename: Yiola
authors.initials: Y
authors.lastname: Marcou
authors.forename: Thalia
authors.initials: T
authors.lastname: Michael
authors.forename: Maria
authors.initials: M
authors.lastname: Daniel
authors.forename: Eleni
authors.initials: E
authors.lastname: Kakouri
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Papadopoulos
authors.forename: Simon
authors.initials: S
authors.lastname: Malas
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D003535:Cyprus; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D000076228:MRE11 Homologue Protein