Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma

Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analy...

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Main Authors:	Rendleman, Justin, Antipin, Yevgeniy, Reva, Boris, Adaniel, Christina, Przybylo, Jennifer A., Dutra-Clarke, Ana, Hansen, Nichole, Heguy, Adriana, Huberman, Kety, Borsu, Laetitia, Paltiel, Ora, Ben-Yehuda, Dina, Brown, Jennifer R., Freedman, Arnold S., Sander, Chris, Zelenetz, Andrew, Klein, Robert J., Shao, Yongzhao, Lacher, Mortimer, Vijai, Joseph, Offit, Kenneth, Kirchhoff, Tomas
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092067/

id	pubmed-4092067
recordtype	oai_dc
spelling	pubmed-40920672014-07-18 Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma Rendleman, Justin Antipin, Yevgeniy Reva, Boris Adaniel, Christina Przybylo, Jennifer A. Dutra-Clarke, Ana Hansen, Nichole Heguy, Adriana Huberman, Kety Borsu, Laetitia Paltiel, Ora Ben-Yehuda, Dina Brown, Jennifer R. Freedman, Arnold S. Sander, Chris Zelenetz, Andrew Klein, Robert J. Shao, Yongzhao Lacher, Mortimer Vijai, Joseph Offit, Kenneth Kirchhoff, Tomas Research Article Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13–1.43, p = 6.77×10−5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34–0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL. Public Library of Science 2014-07-10 /pmc/articles/PMC4092067/ /pubmed/25010664 http://dx.doi.org/10.1371/journal.pone.0101685 Text en © 2014 Rendleman et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rendleman, Justin Antipin, Yevgeniy Reva, Boris Adaniel, Christina Przybylo, Jennifer A. Dutra-Clarke, Ana Hansen, Nichole Heguy, Adriana Huberman, Kety Borsu, Laetitia Paltiel, Ora Ben-Yehuda, Dina Brown, Jennifer R. Freedman, Arnold S. Sander, Chris Zelenetz, Andrew Klein, Robert J. Shao, Yongzhao Lacher, Mortimer Vijai, Joseph Offit, Kenneth Kirchhoff, Tomas
spellingShingle	Rendleman, Justin Antipin, Yevgeniy Reva, Boris Adaniel, Christina Przybylo, Jennifer A. Dutra-Clarke, Ana Hansen, Nichole Heguy, Adriana Huberman, Kety Borsu, Laetitia Paltiel, Ora Ben-Yehuda, Dina Brown, Jennifer R. Freedman, Arnold S. Sander, Chris Zelenetz, Andrew Klein, Robert J. Shao, Yongzhao Lacher, Mortimer Vijai, Joseph Offit, Kenneth Kirchhoff, Tomas Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
author_facet	Rendleman, Justin Antipin, Yevgeniy Reva, Boris Adaniel, Christina Przybylo, Jennifer A. Dutra-Clarke, Ana Hansen, Nichole Heguy, Adriana Huberman, Kety Borsu, Laetitia Paltiel, Ora Ben-Yehuda, Dina Brown, Jennifer R. Freedman, Arnold S. Sander, Chris Zelenetz, Andrew Klein, Robert J. Shao, Yongzhao Lacher, Mortimer Vijai, Joseph Offit, Kenneth Kirchhoff, Tomas
author_sort	Rendleman, Justin
title	Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
title_short	Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
title_full	Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
title_fullStr	Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
title_full_unstemmed	Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma
title_sort	genetic variation in dna repair pathways and risk of non-hodgkin's lymphoma
description	Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13–1.43, p = 6.77×10−5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34–0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092067/
_version_	1613111458742140928

Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma

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