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Breast Cancer Risk is not Associated with Polymorphic Forms of Xeroderma Pigmentosum Genes in a Cohort of Women from Washington County, Maryland

  • Epidemiology
  • Published:
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Abstract

Background

The genes mutated in the cancer-prone syndrome, xeroderma pigmentosum (XP genes), have been well studied both biochemically and mechanistically. These genes are important components of the DNA nucleotide excision repair (NER) pathway, which protects against environmentally-induced cancers. XP genes are also downstream of the hereditary breast cancer syndrome gene, BRCA1, suggesting that XP genes may be important to hereditary forms of breast cancer as well. Although mutated XP genes are rare, polymorphic forms with potential functional deficiencies are common, and could pose a significant cancer risk in the general population.

Hypothesis

This study tested the hypothesis that common polymorphic variants of XP genes were associated with the risk of breast cancer among a population of women in Washington County, Maryland.

Methods

Five single nucleotide polymorphisms (SNPs) among four XP genes (XPC, XPD, XPF and XPG) were genotyped from DNA samples collected at baseline, and then analyzed by conditional logistic regression for association with the incidence of breast cancer. 321 cases were individually matched to 321 controls, by age and menopausal status.

Results

No significant associations were found between breast cancer risk and any of the XP genotypes. Odds ratios for all genotypes ranged from 0.61 to 1.14, and none were statistically significant. Adjustment and stratification for family history of breast cancer did not alter the findings.

Conclusion

These results suggest that polymorphisms of XP genes are not likely to be significant risk factors for women within the general population. This study did not address, however, risks for subpopulations of women with high exposures to DNA damaging agents.

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Acknowledgements

Grant Support: Research was funded by a National Cancer Institute Breast Spore Award (P50 CA88843), and the National Institute of Aging 5U01AG018033. T.J.J. was funded by an NIH Ruth L. Kirschstein Senior Fellow Award (NCI F33 CA09817-01). K.V. is a recipient an ASCO Career Development Award and an NIH Preventive Oncology Academic Award (NCI K07 CA111948). 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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Authors and Affiliations

  1. Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, TRB Room E212, Washington, DC, 20057, USA

    T. J. Jorgensen

  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    K. Visvanathan, L. Thuita, S. Hoffman & K. J. Helzlsouer

  3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    I. Ruczinski

  4. George W. Comstock Center for Public Health Research and Prevention, Hagerstown, MD, USA

    S. Hoffman & K. J. Helzlsouer

  5. The Prevention and Research Center, Mercy Medical Center, Baltimore, MD, USA

    K. J. Helzlsouer

Authors
  1. T. J. Jorgensen
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  2. K. Visvanathan
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  3. I. Ruczinski
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  4. L. Thuita
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  5. S. Hoffman
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  6. K. J. Helzlsouer
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Corresponding author

Correspondence to T. J. Jorgensen.

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Jorgensen, T.J., Visvanathan, K., Ruczinski, I. et al. Breast Cancer Risk is not Associated with Polymorphic Forms of Xeroderma Pigmentosum Genes in a Cohort of Women from Washington County, Maryland. Breast Cancer Res Treat 101, 65–71 (2007). https://doi.org/10.1007/s10549-006-9263-3

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  • DOI: https://doi.org/10.1007/s10549-006-9263-3

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