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Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut

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Abstract

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case–control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13–1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99–2.09; P = 0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56–0.91; P = 0.007) and DLBCL (OR: 0.66; 95% CI: 0.45–0.95; P = 0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.

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Acknowledgements

This study was supported by the NIH grant CA62006 (T. Zheng) and in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. We thank Dr. Bingshu Eric Chen for the statistical consultation for this study.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, 20892, USA

    Min Shen, Qing Lan, Shelia H. Zahm, Sophia S. Wang, Meredith Yeager, Robert Welch, Daehee Kang, Stephen Chanock & Nathaniel Rothman

  2. Department of Epidemiology and Public Health, Yale University, New Haven, CT, 06510, USA

    Tongzhang Zheng, Yawei Zhang, Theodore R. Holford, Brian Leaderer & Yong Zhu

  3. International Agency for Research on Cancer, Lyon, France

    Peter Boyle

  4. Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada

    Bing Zhang

  5. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06520, USA

    Kaiyong Zou

  6. Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, MD, 20892, USA

    Stephen Chanock

Authors
  1. Min Shen
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  2. Tongzhang Zheng
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  3. Qing Lan
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  4. Yawei Zhang
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  5. Shelia H. Zahm
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  6. Sophia S. Wang
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  7. Theodore R. Holford
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  9. Meredith Yeager
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  10. Robert Welch
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  11. Daehee Kang
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  12. Peter Boyle
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  13. Bing Zhang
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  14. Kaiyong Zou
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  15. Yong Zhu
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  16. Stephen Chanock
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  17. Nathaniel Rothman
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Correspondence to Min Shen.

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Shen, M., Zheng, T., Lan, Q. et al. Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut. Hum Genet 119, 659–668 (2006). https://doi.org/10.1007/s00439-006-0177-2

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  • DOI: https://doi.org/10.1007/s00439-006-0177-2

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