Breast Cancer Research and Treatment

, Volume 95, Issue 1, pp 73–80 | Cite as

Polymorphisms of the DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer

  • A.M. Brewster
  • T.J. Jorgensen
  • I. Ruczinski
  • H.Y. Huang
  • S. Hoffman
  • L. Thuita
  • C. Newschaffer
  • R.M. Lunn
  • D. Bell
  • K.J. Helzlsouer


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.

Key words:

breast cancer risk DNA repair genes family history of breast cancer imputation methods nested case–control XPD polymorphisms XRCC1 polymorphisms 


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Grant Support: The National Cancer Institute Breast Spore P50CA88843, and the National Institute of Aging 5U01AG018033. A.M.B was supported by Minority Supplement of Clinical Oncology Research Career Development Program (K12-CA01709) from the National Cancer Institute. T.J.J. was funded by a Ruth L. Kirschstein Senior Fellow Award (NCI F33 CA09817–01). I.R. was supported, in part, by the Maryland Cigarette Restitution Fund Research Grant to the Johns Hopkins Medical Institutions and NIH Grant CA 074841.


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Copyright information

© Springer 2005

Authors and Affiliations

  • A.M. Brewster
    • 1
    • 8
  • T.J. Jorgensen
    • 2
  • I. Ruczinski
    • 3
  • H.Y. Huang
    • 4
  • S. Hoffman
    • 4
  • L. Thuita
    • 4
  • C. Newschaffer
    • 4
  • R.M. Lunn
    • 5
  • D. Bell
    • 6
  • K.J. Helzlsouer
    • 4
    • 7
  1. 1.Department of Clinical Cancer PreventionUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Radiation MedicineGeorgetown University Medical CenterWashington, DCUSA
  3. 3.Department of BiostatisticsJohns Hopkins Bloomberg School of Public Health, Johns Mopkins University School of MedicineBaltimoreUSA
  4. 4.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  5. 5.Toxicology Operations BranchNational Institute of Environmental Health SciencesResearch Triangle ParkUSA
  6. 6.Environmental Genomics SectionNational Institute of Environmental Health SciencesResearch Triangle ParkUSA
  7. 7.The Prevention and Research CenterMercy Medical CenterBaltimoreUSA
  8. 8.Department of Clinical Cancer Prevention, Unit 1360University of Texas, M.D. Anderson Cancer CenterHoustonUSA

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