title: Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal radiosensitivity.
abstract: As enhanced chromosomal radiosensitivity (CRS) results from non- or misrepaired double strand breaks (DSBs) and is a hallmark for breast cancer and single nucleotide polymorphisms (SNPs) in DSB repair genes, such as non homologous end-joining (NHEJ) genes, could be involved in CRS and genetic predisposition to breast cancer. In this study, we investigated the association of five SNPs in three different NHEJ genes with breast cancer in a population-based case-control setting. The total patient population composed of a selected group of patients with a family history of the disease and an unselected group, consisting mainly of sporadic cases. SNP analysis showed that the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] has a significant, positive odds ratio (OR) of 2.81 (95% confidence interval (CI): 1.30-6.05) for the heterozygous (He) and homozygous variant (HV) genotypes in the selected patient group. For the c.-1310 C>G SNP (XRCC6Ku70)[corrected] a significant OR of 1.85 (95%CI: 1.01-3.41) was found for the He genotype in the unselected patient group. On the contrary, the HV genotype of c.1781G>T (XRCC6Ku70) [corrected] displays a significant, negative OR of 0.43 (95%CI: 0.18-0.99) in the total patient population. The He+HV genotypes of the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] also showed high and significant ORs in the group of "radiosensitive," familial breast cancer patients. In conclusion, our results provide preliminary evidence that the variant allele of c.-1310C>G (XRCC6Ku70) [corrected]and c.2099-2408G>A (XRCC5Ku80) [corrected] are risk alleles for breast cancer as well as CRS. The HV genotype of c.1781G>T (XRCC6Ku70) [corrected] on the contrary, seems to protect against breast cancer and ionizing radiation induced micronuclei.
authors.affiliation: Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University, Ghent, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Willems
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.forename: Ans
authors.initials: A
authors.lastname: Baeyens
authors.forename: Veerle
authors.initials: V
authors.lastname: Vandersickel
authors.forename: Joke
authors.initials: J
authors.lastname: Werbrouck
authors.forename: Kim
authors.initials: K
authors.lastname: De Ruyck
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Rudy
authors.initials: R
authors.lastname: Van den Broecke
authors.forename: Amin
authors.initials: A
authors.lastname: Makar
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marras
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Perletti
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
authors.forename: Anne
authors.initials: A
authors.lastname: Vral
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*; D012307:Risk Factors