title: Polymorphisms of the DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer.
abstract: Family history is a risk factor for breast cancer and could be due to shared environmental factors or polymorphisms of cancer susceptibility genes. Deficient function of DNA repair enzymes may partially explain familial risk as polymorphisms of DNA repair genes have been associated, although inconsistently, with breast cancer. This population based case-control study examined the association between polymorphisms in XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp) genes, and breast cancer. Breast cancer cases (n=321) and controls (n=321) were matched on age and menopausal status. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The analysis was conducted omitting observations with missing data, and by using imputation methods to handle missing data. No significant association was observed between the XPD 751Gln/Lys (OR 1.37, 95% CI 0.96-1.96) and Gln/Gln genotypes (OR 1.08, 95% CI 0.62-1.86) (referent Lys/Lys), XRCC1 399Arg/Gln (OR 1.48, 95% CI 0.92-2.38) and Gln/Gln genotypes (1.11, 95% CI 0.67-1.83) (referent Arg/Arg) or the XRCC1 Arg/Trp and Trp/Trp genotypes (OR 1.12, 95% CI 0.69-1.83) (referent Arg/Arg) and breast cancer. In multivariate analysis, the adjusted odds ratios for the XPD and XRCC1 399 polymorphisms increased and became statistically significant, however, were attenuated when imputation methods were used to handle missing data. There was no interaction with family history. These results indicate that these polymorphisms in XPD and XRCC1 genes are only weakly associated with breast cancer. Without imputation methods for handling missing data, a statistically significant association was observed between the genotypes and breast cancer, illustrating the potential for bias in studies that inadequately handle missing data.
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA. abrewster@mdanderson.org
authors.forename: A M
authors.initials: AM
authors.lastname: Brewster
authors.forename: T J
authors.initials: TJ
authors.lastname: Jorgensen
authors.forename: I
authors.initials: I
authors.lastname: Ruczinski
authors.forename: H Y
authors.initials: HY
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: L
authors.initials: L
authors.lastname: Thuita
authors.forename: C
authors.initials: C
authors.lastname: Newschaffer
authors.forename: R M
authors.initials: RM
authors.lastname: Lunn
authors.forename: D
authors.initials: D
authors.lastname: Bell
authors.forename: K J
authors.initials: KJ
authors.lastname: Helzlsouer
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein