| Literature DB >> 25027329 |
Zhaoming Wang1, Bin Zhu2, Mingfeng Zhang2, Hemang Parikh2, Jinping Jia2, Charles C Chung1, Joshua N Sampson2, Jason W Hoskins2, Amy Hutchinson1, Laurie Burdette1, Abdisamad Ibrahim2, Christopher Hautman1, Preethi S Raj2, Christian C Abnet2, Andrew A Adjei3, Anders Ahlbom4, Demetrius Albanes2, Naomi E Allen5, Christine B Ambrosone6, Melinda Aldrich7, Pilar Amiano8, Christopher Amos9, Ulrika Andersson10, Gerald Andriole11, Irene L Andrulis12, Cecilia Arici13, Alan A Arslan14, Melissa A Austin15, Dalsu Baris2, Donald A Barkauskas16, Bryan A Bassig17, Laura E Beane Freeman2, Christine D Berg18, Sonja I Berndt2, Pier Alberto Bertazzi19, Richard B Biritwum3, Amanda Black2, William Blot20, Heiner Boeing21, Paolo Boffetta22, Kelly Bolton23, Marie-Christine Boutron-Ruault24, Paige M Bracci25, Paul Brennan26, Louise A Brinton2, Michelle Brotzman27, H Bas Bueno-de-Mesquita28, Julie E Buring29, Mary Ann Butler30, Qiuyin Cai7, Geraldine Cancel-Tassin31, Federico Canzian32, Guangwen Cao33, Neil E Caporaso2, Alfredo Carrato34, Tania Carreon30, Angela Carta12, Gee-Chen Chang35, I-Shou Chang36, Jenny Chang-Claude32, Xu Che37, Chien-Jen Chen38, Chih-Yi Chen39, Chung-Hsing Chen36, Constance Chen40, Kuan-Yu Chen41, Yuh-Min Chen42, Anand P Chokkalingam43, Lisa W Chu44, Francoise Clavel-Chapelon45, Graham A Colditz46, Joanne S Colt2, David Conti16, Michael B Cook2, Victoria K Cortessis16, E David Crawford47, Olivier Cussenot48, Faith G Davis49, Immaculata De Vivo50, Xiang Deng1, Ti Ding51, Colin P Dinney52, Anna Luisa Di Stefano53, W Ryan Diver54, Eric J Duell55, Joanne W Elena56, Jin-Hu Fan57, Heather Spencer Feigelson58, Maria Feychting4, Jonine D Figueroa2, Adrienne M Flanagan59, Joseph F Fraumeni2, Neal D Freedman2, Brooke L Fridley60, Charles S Fuchs61, Manuela Gago-Dominguez62, Steven Gallinger63, Yu-Tang Gao64, Susan M Gapstur54, Montserrat Garcia-Closas65, Reina Garcia-Closas66, Julie M Gastier-Foster67, J Michael Gaziano68, Daniela S Gerhard69, Carol A Giffen70, Graham G Giles71, Elizabeth M Gillanders72, Edward L Giovannucci73, Michael Goggins74, Nalan Gokgoz75, Alisa M Goldstein2, Carlos Gonzalez76, Richard Gorlick77, Mark H Greene2, Myron Gross78, H Barton Grossman52, Robert Grubb79, Jian Gu80, Peng Guan81, Christopher A Haiman82, Goran Hallmans83, Susan E Hankinson84, Curtis C Harris85, Patricia Hartge2, Claudia Hattinger86, Richard B Hayes87, Qincheng He81, Lee Helman88, Brian E Henderson82, Roger Henriksson10, Judith Hoffman-Bolton89, Chancellor Hohensee90, Elizabeth A Holly25, Yun-Chul Hong91, Robert N Hoover2, H Dean Hosgood92, Chin-Fu Hsiao93, Ann W Hsing94, Chao Agnes Hsiung95, Nan Hu2, Wei Hu2, Zhibin Hu96, Ming-Shyan Huang41, David J Hunter97, Peter D Inskip2, Hidemi Ito98, Eric J Jacobs54, Kevin B Jacobs99, Mazda Jenab26, Bu-Tian Ji2, Christoffer Johansen100, Mattias Johansson101, Alison Johnson102, Rudolf Kaaks32, Ashish M Kamat52, Aruna Kamineni103, Margaret Karagas9, Chand Khanna88, Kay-Tee Khaw104, Christopher Kim2, In-Sam Kim105, Jin Hee Kim106, Yeul Hong Kim107, Young-Chul Kim108, Young Tae Kim109, Chang Hyun Kang109, Yoo Jin Jung109, Cari M Kitahara2, Alison P Klein110, Robert Klein111, Manolis Kogevinas112, Woon-Puay Koh113, Takashi Kohno114, Laurence N Kolonel115, Charles Kooperberg90, Christian P Kratz2, Vittorio Krogh116, Hideo Kunitoh117, Robert C Kurtz111, Nilgun Kurucu118, Qing Lan2, Mark Lathrop119, Ching C Lau120, Fernando Lecanda121, Kyoung-Mu Lee122, Maxwell P Lee88, Loic Le Marchand115, Seth P Lerner123, Donghui Li124, Linda M Liao2, Wei-Yen Lim125, Dongxin Lin126, Jie Lin80, Sara Lindstrom40, Martha S Linet2, Jolanta Lissowska127, Jianjun Liu128, Börje Ljungberg129, Josep Lloreta130, Daru Lu131, Jing Ma132, Nuria Malats133, Satu Mannisto134, Neyssa Marina135, Giuseppe Mastrangelo136, Keitaro Matsuo137, Katherine A McGlynn2, Roberta McKean-Cowdin80, Lorna H McNeill138, Robert R McWilliams139, Beatrice S Melin10, Paul S Meltzer88, James E Mensah3, Xiaoping Miao140, Dominique S Michaud141, Alison M Mondul2, Lee E Moore2, Kenneth Muir142, Shelley Niwa27, Sara H Olson143, Nick Orr144, Salvatore Panico145, Jae Yong Park146, Alpa V Patel54, Ana Patino-Garcia121, Sofia Pavanello136, Petra H M Peeters147, Beata Peplonska148, Ulrike Peters90, Gloria M Petersen139, Piero Picci86, Malcolm C Pike149, Stefano Porru13, Jennifer Prescott50, Xia Pu80, Mark P Purdue2, You-Lin Qiao150, Preetha Rajaraman2, Elio Riboli151, Harvey A Risch152, Rebecca J Rodabough90, Nathaniel Rothman2, Avima M Ruder30, Jeong-Seon Ryu153, Marc Sanson53, Alan Schned9, Fredrick R Schumacher82, Ann G Schwartz154, Kendra L Schwartz155, Molly Schwenn156, Katia Scotlandi86, Adeline Seow125, Consol Serra157, Massimo Serra86, Howard D Sesso29, Gianluca Severi71, Hongbing Shen96, Min Shen2, Sanjay Shete158, Kouya Shiraishi114, Xiao-Ou Shu7, Afshan Siddiq159, Luis Sierrasesumaga121, Sabina Sierri160, Alan Dart Loon Sihoe161, Debra T Silverman2, Matthias Simon162, Melissa C Southey163, Logan Spector164, Margaret Spitz165, Meir Stampfer132, Par Stattin129, Mariana C Stern82, Victoria L Stevens54, Rachael Z Stolzenberg-Solomon2, Daniel O Stram82, Sara S Strom166, Wu-Chou Su167, Malin Sund168, Sook Whan Sung169, Anthony Swerdlow170, Wen Tan126, Hideo Tanaka98, Wei Tang2, Ze-Zhang Tang51, Adonina Tardon171, Evelyn Tay3, Philip R Taylor2, Yao Tettey3, David M Thomas172, Roberto Tirabosco173, Anne Tjonneland174, Geoffrey S Tobias2, Jorge R Toro2, Ruth C Travis5, Dimitrios Trichopoulos175, Rebecca Troisi2, Ann Truelove27, Ying-Huang Tsai176, Margaret A Tucker2, Rosario Tumino177, David Van Den Berg82, Stephen K Van Den Eeden178, Roel Vermeulen179, Paolo Vineis180, Kala Visvanathan89, Ulla Vogel181, Chaoyu Wang2, Chengfeng Wang37, Junwen Wang182, Sophia S Wang183, Elisabete Weiderpass184, Stephanie J Weinstein2, Nicolas Wentzensen2, William Wheeler70, Emily White90, John K Wiencke185, Alicja Wolk186, Brian M Wolpin61, Maria Pik Wong187, Margaret Wrensch185, Chen Wu126, Tangchun Wu136, Xifeng Wu80, Yi-Long Wu188, Jay S Wunder11, Yong-Bing Xiang64, Jun Xu189, Hannah P Yang2, Pan-Chyr Yang41, Yasushi Yatabe190, Yuanqing Ye80, Edward D Yeboah3, Zhihua Yin81, Chen Ying125, Chong-Jen Yu167, Kai Yu2, Jian-Min Yuan191, Krista A Zanetti56, Anne Zeleniuch-Jacquotte192, Wei Zheng7, Baosen Zhou81, Lisa Mirabello2, Sharon A Savage2, Peter Kraft193, Stephen J Chanock1, Meredith Yeager1, Maria Terese Landi2, Jianxin Shi2, Nilanjan Chatterjee2, Laufey T Amundadottir194.
Abstract
Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.Entities:
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Year: 2014 PMID： 25027329 PMCID： PMC4240198 DOI： 10.1093/hmg/ddu363
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150