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

Mitchell J Machiela Qing Lan Susan L Slager Roel C H Vermeulen Lauren R Teras Nicola J Camp James R Cerhan John J Spinelli Sophia S Wang Alexandra Nieters Joseph Vijai Meredith Yeager Zhaoming Wang Hervé Ghesquières James McKay Lucia Conde Paul I W de Bakker David G Cox Laurie Burdett Alain Monnereau Christopher R Flowers Anneclaire J De Roos Angela R Brooks-Wilson Graham G Giles Mads Melbye Jian Gu Rebecca D Jackson Eleanor Kane Mark P Purdue Claire M Vajdic Demetrius Albanes Rachel S Kelly Mariagrazia Zucca Kimberly A Bertrand Anne Zeleniuch-Jacquotte Charles Lawrence Amy Hutchinson Degui Zhi Thomas M Habermann Brian K Link Anne J Novak Ahmet Dogan Yan W Asmann Mark Liebow Carrie A Thompson Stephen M Ansell Thomas E Witzig Hervé Tilly Corinne Haioun Thierry J Molina Henrik Hjalgrim Bengt Glimelius Hans-Olov Adami Göran Roos Paige M Bracci Jacques Riby Martyn T Smith Elizabeth A Holly Wendy Cozen Patricia Hartge Lindsay M Morton Richard K Severson Lesley F Tinker Kari E North Nikolaus Becker Yolanda Benavente Paolo Boffetta Paul Brennan Lenka Foretova Marc Maynadie Anthony Staines Tracy Lightfoot Simon Crouch Alex Smith Eve Roman W Ryan Diver Kenneth Offit Andrew Zelenetz Robert J Klein Danylo J Villano Tongzhang Zheng Yawei Zhang Theodore R Holford Jenny Turner Melissa C Southey Jacqueline Clavel Jarmo Virtamo Stephanie Weinstein Elio Riboli Paolo Vineis Rudolph Kaaks Heiner Boeing Anne Tjønneland Emanuele Angelucci Simonetta Di Lollo Marco Rais Immaculata De Vivo Edward Giovannucci Peter Kraft Jinyan Huang Baoshan Ma Yuanqing Ye Brian C H Chiu Liming Liang Ju-Hyun Park Charles C Chung Dennis D Weisenburger Joseph F Fraumeni Gilles Salles Martha Glenn Lisa Cannon-Albright Karen Curtin Xifeng Wu Karin E Smedby Silvia de Sanjose Christine F Skibola Sonja I Berndt Brenda M Birmann Stephen J Chanock Nathaniel Rothman

Hum Mol Genet 2016 Apr 9;25(8):1663-76. Epub 2016 Feb 9.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

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.

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