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

• Authors: 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; GHESQUIERES Hervé; MCKAY James; CONDE Lucia; BAKKER Paul I. W. de; COX David G.; BURDETT Laurie; MONNEREAU Alain; FLOWERS Christopher R.; ROOS Anneclaire J. De; BROOKS-WILSON Angela R.; GILES Graham G.; MELBYE Mads; GU Jian; JACKSON Rebecca D.; KANE Eleanor; 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.; TILLE 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; FORETOVÁ Lenka; MAYNADIE Marc; STAINES Anthony; LIGHTFOOT Tracy; CROUCH Simon; SMITH Alex; ROMAN Eve; 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; TJONNELAND Anne; ANGELUCCI Emanuele; LOLLO Simonetta Di; RAIS Marco; VIVO Immaculata De; 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 JR Joseph F.; SALLES Gilles; GLENN Martha; CANNON-ALBRIGHT Lisa; CURTIN Karen; WU Xifeng; SMEDBY Karin E.; SANJOSE Silvia de; SKIBOLA Christine F.; BERNDT Sonja I.; BIRMANN Brenda M.; CHANOCK Stephen J.; ROTHMAN Nathaniel
• Year of publication: 2016
• Type: Article in Periodical
• Magazine / Source: Human molecular genetics
• MU Faculty or unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1093/hmg/ddw027
• Field: Oncology and hematology
• Keywords: GENOME-WIDE ASSOCIATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; MENDELIAN RANDOMIZATION; EPIDEMIOLOGIC RESEARCH; SUSCEPTIBILITY LOCI; CANCER-RISK; HLA REGION; CLASSIFICATION; DYSFUNCTION; NEOPLASMS
• Description: 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 x 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 x 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.