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Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study

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Abstract

Objective

DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk.

Methods

Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 single-nucleotide polymorphisms (SNPs) in nine DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer.

Results

There were no associations between these SNPs and overall risk of prostate cancer. Risks by genotype also did not vary by smoking or by family history of prostate cancer. Although two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced-stage tumors when comparing homozygous men carrying the minor versus major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors.

Conclusion

Overall, this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability, a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene–environment interactions may be warranted.

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Acknowledgments

We are grateful to all the men who participated in these studies for their time, effort and cooperation, and interviewers for their help with data collection. This work was supported by NIH grants R01-CA56678, R01-CA092579 and contract N01-CN-05230 from the National Cancer Institute. Additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. Ilir Agalliu was supported by funds from the Albert Einstein College of Medicine of Yeshiva University.

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Author notes

  1. Claudia A. Salinas

    Present address: Division of Hematology and Oncology, University of Michigan Cancer Center, Ann Arbor, MI, 48109, USA

Authors and Affiliations

  1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Ilir Agalliu

  2. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Erika M. Kwon & Elaine A. Ostrander

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., M4-B847, Seattle, WA, 98109-1024, USA

    Claudia A. Salinas, Joseph S. Koopmeiners & Janet L. Stanford

  4. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA

    Claudia A. Salinas & Janet L. Stanford

  5. Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA

    Joseph S. Koopmeiners

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  1. Ilir Agalliu
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  2. Erika M. Kwon
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  5. Elaine A. Ostrander
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  6. Janet L. Stanford
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Corresponding author

Correspondence to Janet L. Stanford.

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Agalliu, I., Kwon, E.M., Salinas, C.A. et al. Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study. Cancer Causes Control 21, 289–300 (2010). https://doi.org/10.1007/s10552-009-9461-5

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  • DOI: https://doi.org/10.1007/s10552-009-9461-5

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