Ying Bao1, Jennifer Prescott1, Chen Yuan2,3, Mingfeng Zhang4, Peter Kraft2,5, Ana Babic3, Vicente Morales-Oyarvide3, Zhi Rong Qian3, Julie E Buring6,7, Barbara B Cochrane8, J Michael Gaziano6,9, Edward L Giovannucci1,2,10, JoAnn E Manson1,2,6, Kimmie Ng3, Shuji Ogino2,3,11, Thomas E Rohan12, Howard D Sesso2,6, Meir J Stampfer1,2,10, Charles S Fuchs1,3, Immaculata De Vivo1,2, Laufey T Amundadottir4, Brian M Wolpin3,13. 1. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. 4. Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 5. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. 6. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 7. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA. 8. University of Washington School of Nursing, Seattle, Washington, USA. 9. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System. 10. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. 11. Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 12. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. 13. Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Abstract
OBJECTIVE: Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. DESIGN: We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. RESULTS: Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). CONCLUSIONS: Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
OBJECTIVE: Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. DESIGN: We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. RESULTS: Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). CONCLUSIONS: Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: K Youngren; E Jeanclos; H Aviv; M Kimura; J Stock; M Hanna; J Skurnick; A Bardeguez; A Aviv Journal: Hum Genet Date: 1998-06 Impact factor: 4.132
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Authors: Sanjay Shete; Fay J Hosking; Lindsay B Robertson; Sara E Dobbins; Marc Sanson; Beatrice Malmer; Matthias Simon; Yannick Marie; Blandine Boisselier; Jean-Yves Delattre; Khe Hoang-Xuan; Soufiane El Hallani; Ahmed Idbaih; Diana Zelenika; Ulrika Andersson; Roger Henriksson; A Tommy Bergenheim; Maria Feychting; Stefan Lönn; Anders Ahlbom; Johannes Schramm; Michael Linnebank; Kari Hemminki; Rajiv Kumar; Sarah J Hepworth; Amy Price; Georgina Armstrong; Yanhong Liu; Xiangjun Gu; Robert Yu; Ching Lau; Minouk Schoemaker; Kenneth Muir; Anthony Swerdlow; Mark Lathrop; Melissa Bondy; Richard S Houlston Journal: Nat Genet Date: 2009-07-05 Impact factor: 38.330
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Authors: Zhaoming Wang; Bin Zhu; Mingfeng Zhang; Hemang Parikh; Jinping Jia; Charles C Chung; Joshua N Sampson; Jason W Hoskins; Amy Hutchinson; Laurie Burdette; Abdisamad Ibrahim; Christopher Hautman; Preethi S Raj; Christian C Abnet; Andrew A Adjei; Anders Ahlbom; Demetrius Albanes; Naomi E Allen; Christine B Ambrosone; Melinda Aldrich; Pilar Amiano; Christopher Amos; Ulrika Andersson; Gerald Andriole; Irene L Andrulis; Cecilia Arici; Alan A Arslan; Melissa A Austin; Dalsu Baris; Donald A Barkauskas; Bryan A Bassig; Laura E Beane Freeman; Christine D Berg; Sonja I Berndt; Pier Alberto Bertazzi; Richard B Biritwum; Amanda Black; William Blot; Heiner Boeing; Paolo Boffetta; Kelly Bolton; Marie-Christine Boutron-Ruault; Paige M Bracci; Paul Brennan; Louise A Brinton; Michelle Brotzman; H Bas Bueno-de-Mesquita; Julie E Buring; Mary Ann Butler; Qiuyin Cai; Geraldine Cancel-Tassin; Federico Canzian; Guangwen Cao; Neil E Caporaso; Alfredo Carrato; Tania Carreon; Angela Carta; Gee-Chen Chang; I-Shou Chang; Jenny Chang-Claude; Xu Che; Chien-Jen Chen; Chih-Yi Chen; Chung-Hsing Chen; Constance Chen; Kuan-Yu Chen; Yuh-Min Chen; Anand P Chokkalingam; Lisa W Chu; Francoise Clavel-Chapelon; Graham A Colditz; Joanne S Colt; David Conti; Michael B Cook; Victoria K Cortessis; E David Crawford; Olivier Cussenot; Faith G Davis; Immaculata De Vivo; Xiang Deng; Ti Ding; Colin P Dinney; Anna Luisa Di Stefano; W Ryan Diver; Eric J Duell; Joanne W Elena; Jin-Hu Fan; Heather Spencer Feigelson; Maria Feychting; Jonine D Figueroa; Adrienne M Flanagan; Joseph F Fraumeni; Neal D Freedman; Brooke L Fridley; Charles S Fuchs; Manuela Gago-Dominguez; Steven Gallinger; Yu-Tang Gao; Susan M Gapstur; Montserrat Garcia-Closas; Reina Garcia-Closas; Julie M Gastier-Foster; J Michael Gaziano; Daniela S Gerhard; Carol A Giffen; Graham G Giles; Elizabeth M Gillanders; Edward L Giovannucci; Michael Goggins; Nalan Gokgoz; Alisa M Goldstein; Carlos Gonzalez; Richard Gorlick; Mark H Greene; Myron Gross; H Barton Grossman; Robert Grubb; Jian Gu; Peng Guan; Christopher A Haiman; Goran Hallmans; Susan E Hankinson; Curtis C Harris; Patricia Hartge; Claudia Hattinger; Richard B Hayes; Qincheng He; Lee Helman; Brian E Henderson; Roger Henriksson; Judith Hoffman-Bolton; Chancellor Hohensee; Elizabeth A Holly; Yun-Chul Hong; Robert N Hoover; H Dean Hosgood; Chin-Fu Hsiao; Ann W Hsing; Chao Agnes Hsiung; Nan Hu; Wei Hu; Zhibin Hu; Ming-Shyan Huang; David J Hunter; Peter D Inskip; Hidemi Ito; Eric J Jacobs; Kevin B Jacobs; Mazda Jenab; Bu-Tian Ji; Christoffer Johansen; Mattias Johansson; Alison Johnson; Rudolf Kaaks; Ashish M Kamat; Aruna Kamineni; Margaret Karagas; Chand Khanna; Kay-Tee Khaw; Christopher Kim; In-Sam Kim; Jin Hee Kim; Yeul Hong Kim; Young-Chul Kim; Young Tae Kim; Chang Hyun Kang; Yoo Jin Jung; Cari M Kitahara; Alison P Klein; Robert Klein; Manolis Kogevinas; Woon-Puay Koh; Takashi Kohno; Laurence N Kolonel; Charles Kooperberg; Christian P Kratz; Vittorio Krogh; Hideo Kunitoh; Robert C Kurtz; Nilgun Kurucu; Qing Lan; Mark Lathrop; Ching C Lau; Fernando Lecanda; Kyoung-Mu Lee; Maxwell P Lee; Loic Le Marchand; Seth P Lerner; Donghui Li; Linda M Liao; Wei-Yen Lim; Dongxin Lin; Jie Lin; Sara Lindstrom; Martha S Linet; Jolanta Lissowska; Jianjun Liu; Börje Ljungberg; Josep Lloreta; Daru Lu; Jing Ma; Nuria Malats; Satu Mannisto; Neyssa Marina; Giuseppe Mastrangelo; Keitaro Matsuo; Katherine A McGlynn; Roberta McKean-Cowdin; Lorna H McNeill; Robert R McWilliams; Beatrice S Melin; Paul S Meltzer; James E Mensah; Xiaoping Miao; Dominique S Michaud; Alison M Mondul; Lee E Moore; Kenneth Muir; Shelley Niwa; Sara H Olson; Nick Orr; Salvatore Panico; Jae Yong Park; Alpa V Patel; Ana Patino-Garcia; Sofia Pavanello; Petra H M Peeters; Beata Peplonska; Ulrike Peters; Gloria M Petersen; Piero Picci; Malcolm C Pike; Stefano Porru; Jennifer Prescott; Xia Pu; Mark P Purdue; You-Lin Qiao; Preetha Rajaraman; Elio Riboli; Harvey A Risch; Rebecca J Rodabough; Nathaniel Rothman; Avima M Ruder; Jeong-Seon Ryu; Marc Sanson; Alan Schned; Fredrick R Schumacher; Ann G Schwartz; Kendra L Schwartz; Molly Schwenn; Katia Scotlandi; Adeline Seow; Consol Serra; Massimo Serra; Howard D Sesso; Gianluca Severi; Hongbing Shen; Min Shen; Sanjay Shete; Kouya Shiraishi; Xiao-Ou Shu; Afshan Siddiq; Luis Sierrasesumaga; Sabina Sierri; Alan Dart Loon Sihoe; Debra T Silverman; Matthias Simon; Melissa C Southey; Logan Spector; Margaret Spitz; Meir Stampfer; Par Stattin; Mariana C Stern; Victoria L Stevens; Rachael Z Stolzenberg-Solomon; Daniel O Stram; Sara S Strom; Wu-Chou Su; Malin Sund; Sook Whan Sung; Anthony Swerdlow; Wen Tan; Hideo Tanaka; Wei Tang; Ze-Zhang Tang; Adonina Tardon; Evelyn Tay; Philip R Taylor; Yao Tettey; David M Thomas; Roberto Tirabosco; Anne Tjonneland; Geoffrey S Tobias; Jorge R Toro; Ruth C Travis; Dimitrios Trichopoulos; Rebecca Troisi; Ann Truelove; Ying-Huang Tsai; Margaret A Tucker; Rosario Tumino; David Van Den Berg; Stephen K Van Den Eeden; Roel Vermeulen; Paolo Vineis; Kala Visvanathan; Ulla Vogel; Chaoyu Wang; Chengfeng Wang; Junwen Wang; Sophia S Wang; Elisabete Weiderpass; Stephanie J Weinstein; Nicolas Wentzensen; William Wheeler; Emily White; John K Wiencke; Alicja Wolk; Brian M Wolpin; Maria Pik Wong; Margaret Wrensch; Chen Wu; Tangchun Wu; Xifeng Wu; Yi-Long Wu; Jay S Wunder; Yong-Bing Xiang; Jun Xu; Hannah P Yang; Pan-Chyr Yang; Yasushi Yatabe; Yuanqing Ye; Edward D Yeboah; Zhihua Yin; Chen Ying; Chong-Jen Yu; Kai Yu; Jian-Min Yuan; Krista A Zanetti; Anne Zeleniuch-Jacquotte; Wei Zheng; Baosen Zhou; Lisa Mirabello; Sharon A Savage; Peter Kraft; Stephen J Chanock; Meredith Yeager; Maria Terese Landi; Jianxin Shi; Nilanjan Chatterjee; Laufey T Amundadottir Journal: Hum Mol Genet Date: 2014-07-15 Impact factor: 6.150
Authors: Mark M Iles; D Timothy Bishop; John C Taylor; Nicholas K Hayward; Myriam Brossard; Anne E Cust; Alison M Dunning; Jeffrey E Lee; Eric K Moses; Lars A Akslen; Per A Andresen; Marie-Françoise Avril; Esther Azizi; Giovanna Bianchi Scarrà; Kevin M Brown; Tadeusz Dębniak; David E Elder; Eitan Friedman; Paola Ghiorzo; Elizabeth M Gillanders; Alisa M Goldstein; Nelleke A Gruis; Johan Hansson; Mark Harland; Per Helsing; Marko Hočevar; Veronica Höiom; Christian Ingvar; Peter A Kanetsky; Maria Teresa Landi; Julie Lang; G Mark Lathrop; Jan Lubiński; Rona M Mackie; Nicholas G Martin; Anders Molven; Grant W Montgomery; Srdjan Novaković; Håkan Olsson; Susana Puig; Joan Anton Puig-Butille; Graham L Radford-Smith; Juliette Randerson-Moor; Nienke van der Stoep; Remco van Doorn; David C Whiteman; Stuart MacGregor; Karen A Pooley; Sarah V Ward; Graham J Mann; Christopher I Amos; Paul D P Pharoah; Florence Demenais; Matthew H Law; Julia A Newton Bishop; Jennifer H Barrett Journal: J Natl Cancer Inst Date: 2014-09-17 Impact factor: 11.816
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