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Title: Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.
Authors: Machiela MJ,  Lan Q,  Slager SL,  Vermeulen RC,  Teras LR,  Camp NJ,  Cerhan JR,  Spinelli JJ,  Wang SS,  Nieters A,  Vijai J,  Yeager M,  Wang Z,  Ghesquières H,  McKay J,  Conde L,  de Bakker PI,  Cox DG,  Burdett L,  Monnereau A,  Flowers CR,  De Roos AJ,  Brooks-Wilson AR,  Giles GG,  Melbye M,  Gu J,  Jackson RD,  Kane E,  Purdue MP,  Vajdic CM,  Albanes D,  Kelly RS,  Zucca M,  Bertrand KA,  Zeleniuch-Jacquotte A,  Lawrence C,  Hutchinson A,  Zhi D,  Habermann TM,  Link BK,  Novak AJ,  Dogan A,  Asmann YW,  Liebow M,  Thompson CA,  Ansell SM,  Witzig TE,  Tilly H,  Haioun C,  Molina TJ,  Hjalgrim H,  Glimelius B,  Adami HO,  Roos G,  Bracci PM,  Riby J,  Smith MT,  Holly EA,  Cozen W,  Hartge P,  Morton LM,  Severson RK,  Tinker LF,  North KE,  Becker N,  Benavente Y,  Boffetta P,  Brennan P,  Foretova L,  Maynadie M,  Staines A,  Lightfoot T,  Crouch S,  Smith A,  Roman E,  Diver WR,  Offit K,  Zelenetz A,  Klein RJ,  Villano DJ,  Zheng T,  Zhang Y,  Holford TR,  Turner J,  Southey MC,  Clavel J,  Virtamo J,  Weinstein S,  Riboli E,  Vineis P,  Kaaks R,  Boeing H,  Tjønneland A,  Angelucci E,  Di Lollo S,  Rais M,  De Vivo I,  Giovannucci E,  Kraft P,  Huang J,  Ma B,  Ye Y,  Chiu BC,  Liang L,  Park JH,  Chung CC,  Weisenburger DD,  Fraumeni JF Jr,  Salles G,  Glenn M,  Cannon-Albright L,  Curtin K,  Wu X,  Smedby KE,  de Sanjose S,  Skibola CF,  Berndt SI,  Birmann BM,  Chanock SJ,  Rothman N
Journal: Hum Mol Genet
Date: 2016 Apr 15
PubMed ID: 27008888
PMC ID: PMC4854019
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.