Dataset Information

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.

SUBMITTER: Machiela MJ

PROVIDER: S-EPMC4854019 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

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

Human molecular genetics 20160209 8

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 ...[more]

PMID: 27008888

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Project description:BackgroundRelative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.ObjectiveWe performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Design, setting, and participantsGenotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.Outcome measurements and statistical analysisOdds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.Results and limitationsLonger genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).ConclusionsOur investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.Patient summaryTelomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

Dataset Information

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

Publications

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

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