Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Abstract

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Metadata

Item Type:	Article
Authors/Creators:	Machiela, Mitchell J Lan, Qing Slager, Susan L Vermeulen, Roel C H Teras, Lauren R Camp, Nicola J Cerhan, James R Spinelli, John J Wang, Sophia S Nieters, Alexandra Vijai, Joseph Yeager, Meredith Wang, Zhaoming Ghesquières, Hervé McKay, James Conde, Lucia de Bakker, Paul I W Cox, David G Burdett, Laurie Monnereau, Alain Flowers, Christopher R De Roos, Anneclaire J Brooks-Wilson, Angela R Giles, Graham G Melbye, Mads Gu, Jian Jackson, Rebecca D Kane, Eleanor https://orcid.org/0000-0002-7438-9982 Purdue, Mark P Vajdic, Claire M Albanes, Demetrius Kelly, Rachel S Zucca, Mariagrazia Bertrand, Kimberly A Zeleniuch-Jacquotte, Anne Lawrence, Charles Hutchinson, Amy Zhi, Degui Habermann, Thomas M Link, Brian K Novak, Anne J Dogan, Ahmet Asmann, Yan W Liebow, Mark Thompson, Carrie A Ansell, Stephen M Witzig, Thomas E Tilly, Hervé Haioun, Corinne Molina, Thierry J Hjalgrim, Henrik Glimelius, Bengt Adami, Hans-Olov Roos, Göran Bracci, Paige M Riby, Jacques Smith, Martyn T Holly, Elizabeth A Cozen, Wendy Hartge, Patricia Morton, Lindsay M Severson, Richard K Tinker, Lesley F North, Kari E Becker, Nikolaus Benavente, Yolanda Boffetta, Paolo Brennan, Paul Foretova, Lenka Maynadie, Marc Staines, Anthony Lightfoot, Tracy https://orcid.org/0000-0003-2869-3438 Crouch, Simon https://orcid.org/0000-0002-3026-2859 Roman, Eve https://orcid.org/0000-0001-7603-3704 Diver, W Ryan Offit, Kenneth Zelenetz, Andrew Klein, Robert J Villano, Danylo J Zheng, Tongzhang Zhang, Yawei Holford, Theodore R Turner, Jenny Southey, Melissa C Clavel, Jacqueline Virtamo, Jarmo Weinstein, Stephanie Riboli, Elio Vineis, Paolo Kaaks, Rudolph Boeing, Heiner Tjønneland, Anne Angelucci, Emanuele Di Lollo, Simonetta Rais, Marco De Vivo, Immaculata Giovannucci, Edward Kraft, Peter Huang, Jinyan Ma, Baoshan Ye, Yuanqing Chiu, Brian C H Liang, Liming Park, Ju-Hyun Chung, Charles C Weisenburger, Dennis D Fraumeni, Joseph F Salles, Gilles Glenn, Martha Cannon-Albright, Lisa Curtin, Karen Wu, Xifeng Smedby, Karin E de Sanjose, Silvia Skibola, Christine F Berndt, Sonja I Birmann, Brenda M Chanock, Stephen J Rothman, Nathaniel Smith, Alexandra Gwen https://orcid.org/0000-0002-1111-966X
Copyright, Publisher and Additional Information:	© 2016, The publisher. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details
Dates:	Published: 15 April 2016 Published (online): 9 February 2016 Accepted: 27 January 2016
Institution:	The University of York
Academic Units:	The University of York > Faculty of Sciences (York) > Health Sciences (York)
Depositing User:	Pure (York)
Date Deposited:	16 May 2016 14:03
Last Modified:	16 Oct 2024 12:56
Published Version:	https://doi.org/10.1093/hmg/ddw027
Status:	Published
Refereed:	Yes
Identification Number:	10.1093/hmg/ddw027
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:99329

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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

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