Polymorphisms in DNA repair genes and risk of non‐Hodgkin lymphoma in a pooled analysis of three studies |
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| Authors: | Min Shen Idan Menashe Lindsay M. Morton Yawei Zhang Bruce Armstrong Sophia S. Wang Qing Lan Patricia Hartge Mark P. Purdue James R. Cerhan Andrew Grulich Wendy Cozen Meredith Yeager Theodore R. Holford Claire M. Vajdic Scott Davis Brian Leaderer Anne Kricker Richard K. Severson Shelia H. Zahm Nilanjan Chatterjee Nathaniel Rothman Stephen J. Chanock Tongzhang Zheng |
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| Affiliation: | 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD;2. MS and IM contributed equally to this work.;3. Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT, USA;4. Sydney School of Public Health, University of Sydney, Sydney, Australia;5. Division of Epidemiology, Mayo Clinic, College of Medicine, Mayo Clinic, Rochester, MN, USA;6. National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia;7. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA;8. Core Genotyping Facility, Advanced Technology Center, NCI, NIH, DHHS, Gaithersburg, MD, USA;9. University of New South Wales Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia;10. Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA;11. Department of Family Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA |
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| Abstract: | Genetic variations in DNA repair genes are thought to play an important role in the pathogenesis and development of non‐Hodgkin lymphoma (NHL). To further explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from three population‐based case‐control studies of NHL in the US and Australia. Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed using logistic regression. Associations of gene regions and pathways with NHL or NHL subtypes were explored using the minP and tail‐strength statistics, respectively. Overall, genetic polymorphisms within the DNA repair pathway were associated with NHL (P = 0·005). Similar associations were seen with the double‐strand break repair (P = 0·02) and nucleotide excision repair (P = 0·04) pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3 rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene regions were significantly associated with NHL or NHL subtypes (minP ≤ 0·05), or because of high level of statistical significance (P ≤ 0·005) and consistent findings across the three studies. These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL. |
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| Keywords: | non‐Hodgkin lymphoma DNA repair single nucleotide polymorphism pooled analysis |
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