title: Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry.
abstract: This study investigates the role of two nonsynonymous single nucleotide polymorphisms in DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1)-R399Q and X-ray repair cross-complementing group 3 (XRCC3)-T241M, in breast cancer. Incident cases of invasive breast cancer in Caucasian women [n = 402, mean age = 45.7 (SD = 6.2) years] and female Caucasian controls [n = 402, mean age = 45.2 (6.5) years] frequency matched on 5-year age intervals were identified from the Ontario Familial Breast Cancer Registry. No evidence for a main effect of the XRCC1-R399Q genotype on breast cancer risk was observed. Estimates of risk for a family history (FH) of breast cancer compared with no FH differed by XRCC1-R399Q genotype (P value for interaction = 0.001). Homozygote XRCC1-399 R/R individuals and FH+ were at a 2.92-fold [95% confidence interval (95% CI) = 1.47-5.79] increased risk of disease compared with FH- individuals; the estimate of risk increased for R/Q heterozygotes with FH+ [odds ratio (OR) = 3.85, 95% CI = 1.94-7.65] but not for Q/Q homozygotes with FH+ (OR = 0.54, 95% CI = 0.20-1.47) compared with homozygous R/R and FH- individuals. A marginal positive association for XRCC3-241 M/M compared with T/T genotype was found (OR = 1.44, 95% CI = 0.94-2.19), but the heterozygous T/M was not associated with an increase in risk (OR = 0.96, 95% CI = 0.71-1.32). There was also some evidence for a combined effect of body mass index and XRCC3-T241M on estimates of risk. Our results suggest that these polymorphisms may influence breast cancer risk by modifying the effect of risk factors such as FH. There is a need for further study into the role of these polymorphisms as effect modifiers.
authors.affiliation: Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Laurent
authors.initials: L
authors.lastname: Briollais
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: Hilmi
authors.initials: H
authors.lastname: Ozcelik
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human