Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3163836 89 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Imputation and subset-based association analysis across different cancer
types identifies multiple independent risk loci in the TERT-CLPTM1L
region on chromosome 5p15.33
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 x
10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and P-Conditional =
2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and P-Conditional
= 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and P-Conditional =
2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10 215 and
P-Conditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L
gene(Region 2: rs451360; P = 1.90 x 10(-18) and P-Conditional = 7.06 x
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.
Έτος δημοσίευσης:
2014
Συγγραφείς:
Wang, Zhaoming
Zhu, Bin
Zhang, Mingfeng
Parikh, Hemang and
Jia, Jinping
Chung, Charles C.
Sampson, Joshua N.
Hoskins,
Jason W.
Hutchinson, Amy
Burdette, Laurie
Ibrahim, Abdisamad
and Hautman, Christopher
Raj, Preethi S.
Abnet, Christian C. and
Adjei, Andrew A.
Ahlbom, Anders
Albanes, Demetrius
Allen,
Naomi E.
Ambrosone, Christine B.
Aldrich, Melinda
Amiano,
Pilar
Amos, Christopher
Andersson, Ulrika
Andriole, Jr.,
Gerald
Andrulis, Irene L.
Arici, Cecilia
Arslan, Alan A. and
Austin, Melissa A.
Baris, Dalsu
Barkauskas, Donald A. and
Bassig, Bryan A.
Freeman, Laura E. Beane
Berg, Christine D. and
Berndt, Sonja I.
Bertazzi, Pier Alberto
Biritwum, Richard B. and
Black, Amanda
Blot, William
Boeing, Heiner
Boffetta, Paolo
and Bolton, Kelly
Boutron-Ruault, Marie-Christine
Bracci, Paige
M.
Brennan, Paul
Brinton, Louise A.
Brotzman, Michelle and
Bueno-de-Mesquita, H. Bas
Buring, Julie E.
Butler, Mary Ann and
Cai, Qiuyin
Cancel-Tassin, Geraldine
Canzian, Federico
Cao,
Guangwen
Caporaso, Neil E.
Carrato, Alfredo
Carreon, Tania
and Carta, Angela
Chang, Gee-Chen
Chang, I-Shou and
Chang-Claude, Jenny
Che, Xu
Chen, Chien-Jen
Chen, Chih-Yi
and Chen, Chung-Hsing
Chen, Constance
Chen, Kuan-Yu
Chen,
Yuh-Min
Chokkalingam, Anand P.
Chu, Lisa W.
Clavel-Chapelon,
Francoise
Colditz, Graham A.
Colt, Joanne S.
Conti, David
and Cook, Michael B.
Cortessis, Victoria K.
Crawford, E. David
and Cussenot, Olivier
Davis, Faith G.
De Vivo, Immaculata and
Deng, Xiang
Ding, Ti
Dinney, Colin P.
Di Stefano, Anna Luisa
and Diver, W. Ryan
Duell, Eric J.
Elena, Joanne W.
Fan,
Jin-Hu
Feigelson, Heather Spencer
Feychting, Maria
Figueroa,
Jonine D.
Flanagan, Adrienne M.
Fraumeni, Jr., Joseph F. and
Freedman, Neal D.
Fridley, Brooke L.
Fuchs, Charles S. and
Gago-Dominguez, Manuela
Gallinger, Steven
Gao, Yu-Tang and
Gapstur, Susan M.
Garcia-Closas, Montserrat
Garcia-Closas, Reina
and Gastier-Foster, Julie M.
Gaziano, J. Michael
Gerhard,
Daniela S.
Giffen, Carol A.
Giles, Graham G.
Gillanders,
Elizabeth M.
Giovannucci, Edward L.
Goggins, Michael
Gokgoz,
Nalan
Goldstein, Alisa M.
Gonzalez, Carlos
Gorlick, Richard
and Greene, Mark H.
Gross, Myron
Grossman, H. Barton
Grubb,
III, Robert
Gu, Jian
Guan, Peng
Haiman, Christopher A. and
Hallmans, Goran
Hankinson, Susan E.
Harris, Curtis C. and
Hartge, Patricia
Hattinger, Claudia
Hayes, Richard B.
He,
Qincheng
Helman, Lee
Henderson, Brian E.
Henriksson, Roger
and Hoffman-Bolton, Judith
Hohensee, Chancellor
Holly, Elizabeth
A.
Hong, Yun-Chul
Hoover, Robert N.
Hosgood, H. Dean and
Hsiao, Chin-Fu
Hsing, Ann W.
Hsiung, Chao Agnes
Hu, Nan and
Hu, Wei
Hu, Zhibin
Huang, Ming-Shyan
Hunter, David J. and
Inskip, Peter D.
Ito, Hidemi
Jacobs, Eric J.
Jacobs, Kevin
B.
Jenab, Mazda
Ji, Bu-Tian
Johansen, Christoffer and
Johansson, Mattias
Johnson, Alison
Kaaks, Rudolf
Kamat,
Ashish M.
Kamineni, Aruna
Karagas, Margaret
Khanna, Chand
and Khaw, Kay-Tee
Kim, Christopher
Kim, In-Sam
Kim, Jin Hee
and Kim, Yeul Hong
Kim, Young-Chul
Kim, Young Tae
Kang,
Chang Hyun
Jung, Yoo Jin
Kitahara, Cari M.
Klein, Alison P.
and Klein, Robert
Kogevinas, Manolis
Koh, Woon-Puay
Kohno,
Takashi
Kolonel, Laurence N.
Kooperberg, Charles
Kratz,
Christian P.
Krogh, Vittorio
Kunitoh, Hideo
Kurtz, Robert C.
and Kurucu, Nilgun
Lan, Qing
Lathrop, Mark
Lau, Ching C. and
Lecanda, Fernando
Lee, Kyoung-Mu
Lee, Maxwell P.
Le
Marchand, Loic
Lerner, Seth P.
Li, Donghui
Liao, Linda M.
and Lim, Wei-Yen
Lin, Dongxin
Lin, Jie
Lindstrom, Sara and
Linet, Martha S.
Lissowska, Jolanta
Liu, Jianjun
Ljungberg,
Boerje
Lloreta, Josep
Lu, Daru
Ma, Jing
Malats, Nuria
and Mannisto, Satu
Marina, Neyssa
Mastrangelo, Giuseppe and
Matsuo, Keitaro
McGlynn, Katherine A.
McKean-Cowdin, Roberta and
McNeill, Lorna H.
McWilliams, Robert R.
Melin, Beatrice S. and
Meltzer, Paul S.
Mensah, James E.
Miao, Xiaoping
Michaud,
Dominique S.
Mondul, Alison M.
Moore, Lee E.
Muir, Kenneth
and Niwa, Shelley
Olson, Sara H.
Orr, Nick
Panico, Salvatore
and Park, Jae Yong
Patel, Alpa V.
Patino-Garcia, Ana and
Pavanello, Sofia
Peeters, Petra H. M.
Peplonska, Beata and
Peters, Ulrike
Petersen, Gloria M.
Picci, Piero
Pike,
Malcolm C.
Porru, Stefano
Prescott, Jennifer
Pu, Xia and
Purdue, Mark P.
Qiao, You-Lin
Rajaraman, Preetha
Riboli,
Elio
Risch, Harvey A.
Rodabough, Rebecca J.
Rothman,
Nathaniel
Ruder, Avima M.
Ryu, Jeong-Seon
Sanson, Marc and
Schned, Alan
Schumacher, Fredrick R.
Schwartz, Ann G. and
Schwartz, Kendra L.
Schwenn, Molly
Scotlandi, Katia
Seow,
Adeline
Serra, Consol
Serra, Massimo
Sesso, Howard D. and
Severi, Gianluca
Shen, Hongbing
Shen, Min
Shete, Sanjay and
Shiraishi, Kouya
Shu, Xiao-Ou
Siddiq, Afshan
Sierrasesumaga,
Luis
Sierri, Sabina
Sihoe, Alan Dart Loon
Silverman, Debra
T.
Simon, Matthias
Southey, Melissa C.
Spector, Logan and
Spitz, Margaret
Stampfer, Meir
Stattin, Par
Stern, Mariana
C.
Stevens, Victoria L.
Stolzenberg-Solomon, Rachael Z. and
Stram, Daniel O.
Strom, Sara S.
Su, Wu-Chou
Sund, Malin and
Sung, Sook Whan
Swerdlow, Anthony
Tan, Wen
Tanaka, Hideo and
Tang, Wei
Tang, Ze-Zhang
Tardon, Adonina
Tay, Evelyn and
Taylor, Philip R.
Tettey, Yao
Thomas, David M.
Tirabosco,
Roberto
Tjonneland, Anne
Tobias, Geoffrey S.
Toro, Jorge R.
and Travis, Ruth C.
Trichopoulos, Dimitrios
Troisi, Rebecca and
Truelove, Ann
Tsai, Ying-Huang
Tucker, Margaret A.
Tumino,
Rosario
Van Den Berg, David
Van Den Eeden, Stephen K. and
Vermeulen, Roel
Vineis, Paolo
Visvanathan, Kala
Vogel, Ulla
and Wang, Chaoyu
Wang, Chengfeng
Wang, Junwen
Wang, Sophia
S.
Weiderpass, Elisabete
Weinstein, Stephanie J.
Wentzensen,
Nicolas
Wheeler, William
White, Emily
Wiencke, John K. and
Wolk, Alicja
Wolpin, Brian M.
Wong, Maria Pik
Wrensch,
Margaret
Wu, Chen
Wu, Tangchun
Wu, Xifeng
Wu, Yi-Long
and Wunder, Jay S.
Xiang, Yong-Bing
Xu, Jun
Yang, Hannah P.
and Yang, Pan-Chyr
Yatabe, Yasushi
Ye, Yuanqing
Yeboah,
Edward D.
Yin, Zhihua
Ying, Chen
Yu, Chong-Jen
Yu, Kai
and Yuan, Jian-Min
Zanetti, Krista A.
Zeleniuch-Jacquotte, Anne
and Zheng, Wei
Zhou, Baosen
Mirabello, Lisa
Savage, Sharon
A.
Kraft, Peter
Chanock, Stephen J.
Yeager, Meredith and
Landi, Maria Terese
Shi, Jianxin
Chatterjee, Nilanjan and
Amundadottir, Laufey T.
Περιοδικό:
Human Molecular Genetics
Εκδότης:
Oxford University Press
Τόμος:
23
Αριθμός / τεύχος:
24
Σελίδες:
6616-6633
Επίσημο URL (Εκδότης):
DOI:
10.1093/hmg/ddu363
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