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

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 AldrichPilar Amiano, Christopher Amos, Ulrika Andersson, G. A. 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. McNeil, Robert R Mc Williams, 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

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 CLPTM1Lgene(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.

Original languageEnglish (US)
Pages (from-to)6616-6633
Number of pages18
JournalHuman Molecular Genetics
Volume23
Issue number24
DOIs
StatePublished - Nov 15 2014

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Chromosomes
Alleles
Neoplasms
Genome-Wide Association Study
Telomerase
DNA Methylation
Methylation
Genes
Single Nucleotide Polymorphism
Meta-Analysis
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

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

In: Human Molecular Genetics, Vol. 23, No. 24, 15.11.2014, p. 6616-6633.

Research output: Contribution to journalArticle

Wang, Z, Zhu, B, Zhang, M, Parikh, H, Jia, J, Chung, CC, Sampson, JN, Hoskins, JW, Hutchinson, A, Burdette, L, Ibrahim, A, Hautman, C, Raj, PS, Abnet, CC, Adjei, AA, Ahlbom, A, Albanes, D, Allen, NE, Ambrosone, CB, Aldrich, M, Amiano, P, Amos, C, Andersson, U, Gerald Andriole, GA, Andrulis, IL, Arici, C, Arslan, AA, Austin, MA, Baris, D, Barkauskas, DA, Bassig, BA, Freeman, LEB, Berg, CD, Berndt, SI, Bertazzi, PA, Biritwum, RB, Black, A, Blot, W, Boeing, H, Boffetta, P, Bolton, K, Boutron-Ruault, MC, Bracci, PM, Brennan, P, Brinton, LA, Brotzman, M, Bueno-de-Mesquita, HB, Buring, JE, Butler, MA, Cai, Q, Cancel-Tassin, G, Canzian, F, Cao, G, Caporaso, NE, Carrato, A, Carreon, T, Carta, A, Chang, GC, Chang, IS, Chang-Claude, J, Che, X, Chen, CJ, Chen, CY, Chen, CH, Chen, C, Chen, KY, Chen, YM, Chokkalingam, AP, Chu, LW, Clavel-Chapelon, F, Colditz, GA, Colt, JS, Conti, D, Cook, MB, Cortessis, VK, Crawford, ED, Cussenot, O, Davis, FG, De Vivo, I, Deng, X, Ding, T, Dinney, CP, Di Stefano, AL, Diver, WR, Duell, EJ, Elena, JW, Fan, JH, Feigelson, HS, Feychting, M, Figueroa, JD, Flanagan, AM, Fraumeni, JF, Freedman, ND, Fridley, BL, Fuchs, CS, Gago-Dominguez, M, Gallinger, S, Gao, YT, Gapstur, SM, Garcia-Closas, M, Garcia-Closas, R, Gastier-Foster, JM, Gaziano, JM, Gerhard, DS, Giffen, CA, Giles, GG, Gillanders, EM, Giovannucci, EL, Goggins, M, Gokgoz, N, Goldstein, AM, Gonzalez, C, Gorlick, R, Greene, MH, Gross, M, Grossman, HB, Grubb, R, Gu, J, Guan, P, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Hartge, P, Hattinger, C, Hayes, RB, He, Q, Helman, L, Henderson, BE, Henriksson, R, Hoffman-Bolton, J, Hohensee, C, Holly, EA, Hong, YC, Hoover, RN, Dean Hosgood, H, Hsiao, CF, Hsing, AW, Hsiung, CA, Hu, N, Hu, W, Hu, Z, Huang, MS, Hunter, DJ, Inskip, PD, Ito, H, Jacobs, EJ, Jacobs, KB, Jenab, M, Ji, BT, Johansen, C, Johansson, M, Johnson, A, Kaaks, R, Kamat, AM, Kamineni, A, Karagas, M, Khanna, C, Khaw, KT, Kim, C, Kim, IS, Kim, JH, Kim, YH, Kim, YC, Kim, YT, Kang, CH, Jung, YJ, Kitahara, CM, Klein, AP, Klein, R, Kogevinas, M, Koh, WP, Kohno, T, Kolonel, LN, Kooperberg, C, Kratz, CP, Krogh, V, Kunitoh, H, Kurtz, RC, Kurucu, N, Lan, Q, Lathrop, M, Lau, CC, Lecanda, F, Lee, KM, Lee, MP, Marchand, LL, Lerner, SP, Li, D, Liao, LM, Lim, WY, Lin, D, Lin, J, Lindstrom, S, Linet, MS, Lissowska, J, Liu, J, Ljungberg, B, Lloreta, J, Lu, D, Ma, J, Malats, N, Mannisto, S, Marina, N, Mastrangelo, G, Matsuo, K, McGlynn, KA, McKean-Cowdin, R, McNeil, LH, Mc Williams, RR, Melin, BS, Meltzer, PS, Mensah, JE, Miao, X, Michaud, DS, Mondul, AM, Moore, LE, Muir, K, Niwa, S, Olson, SH, Orr, N, Panico, S, Park, JY, Patel, AV, Patino-Garcia, A, Pavanello, S, Peeters, PHM, Peplonska, B, Peters, U, Petersen, GM, Picci, P, Pike, MC, Porru, S, Prescott, J, Pu, X, Purdue, MP, Qiao, YL, Rajaraman, P, Riboli, E, Risch, HA, Rodabough, RJ, Rothman, N, Ruder, AM, Ryu, JS, Sanson, M, Schned, A, Schumacher, FR, Schwartz, AG, Schwartz, KL, Schwenn, M, Scotlandi, K, Seow, A, Serra, C, Serra, M, Sesso, HD, Severi, G, Shen, H, Shen, M, Shete, S, Shiraishi, K, Shu, XO, Siddiq, A, Sierrasesumaga, L, Sierri, S, Sihoe, ADL, Silverman, DT, Simon, M, Southey, MC, Spector, L, Spitz, M, Stampfer, M, Stattin, P, Stern, MC, Stevens, VL, Stolzenberg-Solomon, RZ, Stram, DO, Strom, SS, Su, WC, Sund, M, Sung, SW, Swerdlow, A, Tan, W, Tanaka, H, Tang, W, Tang, ZZ, Tardon, A, Tay, E, Taylor, PR, Tettey, Y, Thomas, DM, Tirabosco, R, Tjonneland, A, Tobias, GS, Toro, JR, Travis, RC, Trichopoulos, D, Troisi, R, Truelove, A, Tsai, YH, Tucker, MA, Tumino, R, Van Den Berg, D, Van Den Eeden, SK, Vermeulen, R, Vineis, P, Visvanathan, K, Vogel, U, Wang, C, Wang, C, Wang, J, Wang, SS, Weiderpass, E, Weinstein, SJ, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolk, A, Wolpin, BM, Wong, MP, Wrensch, M, Wu, C, Wu, T, Wu, X, Wu, YL, Wunder, JS, Xiang, YB, Xu, J, Yang, HP, Yang, PC, Yatabe, Y, Ye, Y, Yeboah, ED, Yin, Z, Ying, C, Yu, CJ, Yu, K, Yuan, JM, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Mirabello, L, Savage, SA, Kraft, P, Chanock, SJ, Yeager, M, Landi, MT, Shi, J, Chatterjee, N & Amundadottir, LT 2014, 'Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33', Human Molecular Genetics, vol. 23, no. 24, pp. 6616-6633. https://doi.org/10.1093/hmg/ddu363
Wang, Zhaoming ; Zhu, Bin ; Zhang, Mingfeng ; Parikh, Hemang ; Jia, Jinping ; Chung, Charles C. ; Sampson, Joshua N. ; Hoskins, Jason W. ; Hutchinson, Amy ; Burdette, Laurie ; Ibrahim, Abdisamad ; Hautman, Christopher ; Raj, Preethi S. ; Abnet, Christian C. ; Adjei, Andrew A. ; Ahlbom, Anders ; Albanes, Demetrius ; Allen, Naomi E. ; Ambrosone, Christine B. ; Aldrich, Melinda ; Amiano, Pilar ; Amos, Christopher ; Andersson, Ulrika ; Gerald Andriole, G. A. ; Andrulis, Irene L. ; Arici, Cecilia ; Arslan, Alan A. ; Austin, Melissa A. ; Baris, Dalsu ; Barkauskas, Donald A. ; Bassig, Bryan A. ; Freeman, Laura E Beane ; Berg, Christine D. ; Berndt, Sonja I. ; Bertazzi, Pier Alberto ; Biritwum, Richard B. ; Black, Amanda ; Blot, William ; Boeing, Heiner ; Boffetta, Paolo ; Bolton, Kelly ; Boutron-Ruault, Marie Christine ; Bracci, Paige M. ; Brennan, Paul ; Brinton, Louise A. ; Brotzman, Michelle ; Bueno-de-Mesquita, H. Bas ; Buring, Julie E. ; Butler, Mary Ann ; Cai, Qiuyin ; Cancel-Tassin, Geraldine ; Canzian, Federico ; Cao, Guangwen ; Caporaso, Neil E. ; Carrato, Alfredo ; Carreon, Tania ; Carta, Angela ; Chang, Gee Chen ; Chang, I. Shou ; Chang-Claude, Jenny ; Che, Xu ; Chen, Chien Jen ; Chen, Chih Yi ; 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 ; Cook, Michael B. ; Cortessis, Victoria K. ; Crawford, E. David ; Cussenot, Olivier ; Davis, Faith G. ; De Vivo, Immaculata ; Deng, Xiang ; Ding, Ti ; Dinney, Colin P. ; Di Stefano, Anna Luisa ; Diver, W. Ryan ; Duell, Eric J. ; Elena, Joanne W. ; Fan, Jin Hu ; Feigelson, Heather Spencer ; Feychting, Maria ; Figueroa, Jonine D. ; Flanagan, Adrienne M. ; Fraumeni, Joseph F. ; Freedman, Neal D. ; Fridley, Brooke L. ; Fuchs, Charles S. ; Gago-Dominguez, Manuela ; Gallinger, Steven ; Gao, Yu Tang ; Gapstur, Susan M. ; Garcia-Closas, Montserrat ; Garcia-Closas, Reina ; 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 ; Greene, Mark H. ; Gross, Myron ; Grossman, H. Barton ; Grubb, Robert ; Gu, Jian ; Guan, Peng ; Haiman, Christopher A. ; Hallmans, Goran ; Hankinson, Susan E. ; Harris, Curtis C. ; Hartge, Patricia ; Hattinger, Claudia ; Hayes, Richard B. ; He, Qincheng ; Helman, Lee ; Henderson, Brian E. ; Henriksson, Roger ; Hoffman-Bolton, Judith ; Hohensee, Chancellor ; Holly, Elizabeth A. ; Hong, Yun Chul ; Hoover, Robert N. ; Dean Hosgood, H. ; Hsiao, Chin Fu ; Hsing, Ann W. ; Hsiung, Chao Agnes ; Hu, Nan ; Hu, Wei ; Hu, Zhibin ; Huang, Ming Shyan ; Hunter, David J. ; Inskip, Peter D. ; Ito, Hidemi ; Jacobs, Eric J. ; Jacobs, Kevin B. ; Jenab, Mazda ; Ji, Bu Tian ; Johansen, Christoffer ; Johansson, Mattias ; Johnson, Alison ; Kaaks, Rudolf ; Kamat, Ashish M. ; Kamineni, Aruna ; Karagas, Margaret ; Khanna, Chand ; Khaw, Kay Tee ; Kim, Christopher ; Kim, In Sam ; Kim, Jin Hee ; Kim, Yeul Hong ; Kim, Young Chul ; Kim, Young Tae ; Kang, Chang Hyun ; Jung, Yoo Jin ; Kitahara, Cari M. ; Klein, Alison P. ; Klein, Robert ; Kogevinas, Manolis ; Koh, Woon Puay ; Kohno, Takashi ; Kolonel, Laurence N. ; Kooperberg, Charles ; Kratz, Christian P. ; Krogh, Vittorio ; Kunitoh, Hideo ; Kurtz, Robert C. ; Kurucu, Nilgun ; Lan, Qing ; Lathrop, Mark ; Lau, Ching C. ; Lecanda, Fernando ; Lee, Kyoung Mu ; Lee, Maxwell P. ; Marchand, Loic Le ; Lerner, Seth P. ; Li, Donghui ; Liao, Linda M. ; Lim, Wei Yen ; Lin, Dongxin ; Lin, Jie ; Lindstrom, Sara ; Linet, Martha S. ; Lissowska, Jolanta ; Liu, Jianjun ; Ljungberg, Börje ; Lloreta, Josep ; Lu, Daru ; Ma, Jing ; Malats, Nuria ; Mannisto, Satu ; Marina, Neyssa ; Mastrangelo, Giuseppe ; Matsuo, Keitaro ; McGlynn, Katherine A. ; McKean-Cowdin, Roberta ; McNeil, Lorna H. ; Mc Williams, Robert R ; Melin, Beatrice S. ; Meltzer, Paul S. ; Mensah, James E. ; Miao, Xiaoping ; Michaud, Dominique S. ; Mondul, Alison M. ; Moore, Lee E. ; Muir, Kenneth ; Niwa, Shelley ; Olson, Sara H. ; Orr, Nick ; Panico, Salvatore ; Park, Jae Yong ; Patel, Alpa V. ; Patino-Garcia, Ana ; Pavanello, Sofia ; Peeters, Petra H M ; Peplonska, Beata ; Peters, Ulrike ; Petersen, Gloria M ; Picci, Piero ; Pike, Malcolm C. ; Porru, Stefano ; Prescott, Jennifer ; Pu, Xia ; 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 ; Schned, Alan ; Schumacher, Fredrick R. ; Schwartz, Ann G. ; Schwartz, Kendra L. ; Schwenn, Molly ; Scotlandi, Katia ; Seow, Adeline ; Serra, Consol ; Serra, Massimo ; Sesso, Howard D. ; Severi, Gianluca ; Shen, Hongbing ; Shen, Min ; Shete, Sanjay ; 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 ; Spitz, Margaret ; Stampfer, Meir ; Stattin, Par ; Stern, Mariana C. ; Stevens, Victoria L. ; Stolzenberg-Solomon, Rachael Z. ; Stram, Daniel O. ; Strom, Sara S. ; Su, Wu Chou ; Sund, Malin ; Sung, Sook Whan ; Swerdlow, Anthony ; Tan, Wen ; Tanaka, Hideo ; Tang, Wei ; Tang, Ze Zhang ; Tardon, Adonina ; Tay, Evelyn ; Taylor, Philip R. ; Tettey, Yao ; Thomas, David M. ; Tirabosco, Roberto ; Tjonneland, Anne ; Tobias, Geoffrey S. ; Toro, Jorge R. ; Travis, Ruth C. ; Trichopoulos, Dimitrios ; Troisi, Rebecca ; Truelove, Ann ; Tsai, Ying Huang ; Tucker, Margaret A. ; Tumino, Rosario ; Van Den Berg, David ; Van Den Eeden, Stephen K. ; Vermeulen, Roel ; Vineis, Paolo ; Visvanathan, Kala ; Vogel, Ulla ; Wang, Chaoyu ; Wang, Chengfeng ; Wang, Junwen ; Wang, Sophia S. ; Weiderpass, Elisabete ; Weinstein, Stephanie J. ; Wentzensen, Nicolas ; Wheeler, William ; White, Emily ; Wiencke, John K. ; Wolk, Alicja ; Wolpin, Brian M. ; Wong, Maria Pik ; Wrensch, Margaret ; Wu, Chen ; Wu, Tangchun ; Wu, Xifeng ; Wu, Yi Long ; Wunder, Jay S. ; Xiang, Yong Bing ; Xu, Jun ; Yang, Hannah P. ; Yang, Pan Chyr ; Yatabe, Yasushi ; Ye, Yuanqing ; Yeboah, Edward D. ; Yin, Zhihua ; Ying, Chen ; Yu, Chong Jen ; Yu, Kai ; Yuan, Jian Min ; Zanetti, Krista A. ; Zeleniuch-Jacquotte, Anne ; Zheng, Wei ; Zhou, Baosen ; Mirabello, Lisa ; Savage, Sharon A. ; Kraft, Peter ; Chanock, Stephen J. ; Yeager, Meredith ; Landi, Maria Terese ; Shi, Jianxin ; Chatterjee, Nilanjan ; Amundadottir, Laufey T. / Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 24. pp. 6616-6633.
@article{385638c6e87f48458ce57397eb5514dd,
title = "Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33",
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 CLPTM1Lgene(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.",
author = "Zhaoming Wang and Bin Zhu and Mingfeng Zhang and Hemang Parikh and Jinping Jia and Chung, {Charles C.} and Sampson, {Joshua N.} and Hoskins, {Jason W.} and Amy Hutchinson and Laurie Burdette and Abdisamad Ibrahim and Christopher Hautman and Raj, {Preethi S.} and Abnet, {Christian C.} and Adjei, {Andrew A.} and Anders Ahlbom and Demetrius Albanes and Allen, {Naomi E.} and Ambrosone, {Christine B.} and Melinda Aldrich and Pilar Amiano and Christopher Amos and Ulrika Andersson and {Gerald Andriole}, {G. A.} and Andrulis, {Irene L.} and Cecilia Arici and Arslan, {Alan A.} and Austin, {Melissa A.} and Dalsu Baris and Barkauskas, {Donald A.} and Bassig, {Bryan A.} and Freeman, {Laura E Beane} and Berg, {Christine D.} and Berndt, {Sonja I.} and Bertazzi, {Pier Alberto} and Biritwum, {Richard B.} and Amanda Black and William Blot and Heiner Boeing and Paolo Boffetta and Kelly Bolton and Boutron-Ruault, {Marie Christine} and Bracci, {Paige M.} and Paul Brennan and Brinton, {Louise A.} and Michelle Brotzman and Bueno-de-Mesquita, {H. Bas} and Buring, {Julie E.} and Butler, {Mary Ann} and Qiuyin Cai and Geraldine Cancel-Tassin and Federico Canzian and Guangwen Cao and Caporaso, {Neil E.} and Alfredo Carrato and Tania Carreon and Angela Carta and Chang, {Gee Chen} and Chang, {I. Shou} and Jenny Chang-Claude and Xu Che and Chen, {Chien Jen} and Chen, {Chih Yi} and Chen, {Chung Hsing} and Constance Chen and Chen, {Kuan Yu} and Chen, {Yuh Min} and Chokkalingam, {Anand P.} and Chu, {Lisa W.} and Francoise Clavel-Chapelon and Colditz, {Graham A.} and Colt, {Joanne S.} and David Conti and Cook, {Michael B.} and Cortessis, {Victoria K.} and Crawford, {E. David} and Olivier Cussenot and Davis, {Faith G.} and {De Vivo}, Immaculata and Xiang Deng and Ti Ding and Dinney, {Colin P.} and {Di Stefano}, {Anna Luisa} and Diver, {W. Ryan} and Duell, {Eric J.} and Elena, {Joanne W.} and Fan, {Jin Hu} and Feigelson, {Heather Spencer} and Maria Feychting and Figueroa, {Jonine D.} and Flanagan, {Adrienne M.} and Fraumeni, {Joseph F.} and Freedman, {Neal D.} and Fridley, {Brooke L.} and Fuchs, {Charles S.} and Manuela Gago-Dominguez and Steven Gallinger and Gao, {Yu Tang} and Gapstur, {Susan M.} and Montserrat Garcia-Closas and Reina Garcia-Closas and Gastier-Foster, {Julie M.} and Gaziano, {J. Michael} and Gerhard, {Daniela S.} and Giffen, {Carol A.} and Giles, {Graham G.} and Gillanders, {Elizabeth M.} and Giovannucci, {Edward L.} and Michael Goggins and Nalan Gokgoz and Goldstein, {Alisa M.} and Carlos Gonzalez and Richard Gorlick and Greene, {Mark H.} and Myron Gross and Grossman, {H. Barton} and Robert Grubb and Jian Gu and Peng Guan and Haiman, {Christopher A.} and Goran Hallmans and Hankinson, {Susan E.} and Harris, {Curtis C.} and Patricia Hartge and Claudia Hattinger and Hayes, {Richard B.} and Qincheng He and Lee Helman and Henderson, {Brian E.} and Roger Henriksson and Judith Hoffman-Bolton and Chancellor Hohensee and Holly, {Elizabeth A.} and Hong, {Yun Chul} and Hoover, {Robert N.} and {Dean Hosgood}, H. and Hsiao, {Chin Fu} and Hsing, {Ann W.} and Hsiung, {Chao Agnes} and Nan Hu and Wei Hu and Zhibin Hu and Huang, {Ming Shyan} and Hunter, {David J.} and Inskip, {Peter D.} and Hidemi Ito and Jacobs, {Eric J.} and Jacobs, {Kevin B.} and Mazda Jenab and Ji, {Bu Tian} and Christoffer Johansen and Mattias Johansson and Alison Johnson and Rudolf Kaaks and Kamat, {Ashish M.} and Aruna Kamineni and Margaret Karagas and Chand Khanna and Khaw, {Kay Tee} and Christopher Kim and Kim, {In Sam} and Kim, {Jin Hee} and Kim, {Yeul Hong} and Kim, {Young Chul} and Kim, {Young Tae} and Kang, {Chang Hyun} and Jung, {Yoo Jin} and Kitahara, {Cari M.} and Klein, {Alison P.} and Robert Klein and Manolis Kogevinas and Koh, {Woon Puay} and Takashi Kohno and Kolonel, {Laurence N.} and Charles Kooperberg and Kratz, {Christian P.} and Vittorio Krogh and Hideo Kunitoh and Kurtz, {Robert C.} and Nilgun Kurucu and Qing Lan and Mark Lathrop and Lau, {Ching C.} and Fernando Lecanda and Lee, {Kyoung Mu} and Lee, {Maxwell P.} and Marchand, {Loic Le} and Lerner, {Seth P.} and Donghui Li and Liao, {Linda M.} and Lim, {Wei Yen} and Dongxin Lin and Jie Lin and Sara Lindstrom and Linet, {Martha S.} and Jolanta Lissowska and Jianjun Liu and B{\"o}rje Ljungberg and Josep Lloreta and Daru Lu and Jing Ma and Nuria Malats and Satu Mannisto and Neyssa Marina and Giuseppe Mastrangelo and Keitaro Matsuo and McGlynn, {Katherine A.} and Roberta McKean-Cowdin and McNeil, {Lorna H.} and {Mc Williams}, {Robert R} and Melin, {Beatrice S.} and Meltzer, {Paul S.} and Mensah, {James E.} and Xiaoping Miao and Michaud, {Dominique S.} and Mondul, {Alison M.} and Moore, {Lee E.} and Kenneth Muir and Shelley Niwa and Olson, {Sara H.} and Nick Orr and Salvatore Panico and Park, {Jae Yong} and Patel, {Alpa V.} and Ana Patino-Garcia and Sofia Pavanello and Peeters, {Petra H M} and Beata Peplonska and Ulrike Peters and Petersen, {Gloria M} and Piero Picci and Pike, {Malcolm C.} and Stefano Porru and Jennifer Prescott and Xia Pu and Purdue, {Mark P.} and Qiao, {You Lin} and Preetha Rajaraman and Elio Riboli and Risch, {Harvey A.} and Rodabough, {Rebecca J.} and Nathaniel Rothman and Ruder, {Avima M.} and Ryu, {Jeong Seon} and Marc Sanson and Alan Schned and Schumacher, {Fredrick R.} and Schwartz, {Ann G.} and Schwartz, {Kendra L.} and Molly Schwenn and Katia Scotlandi and Adeline Seow and Consol Serra and Massimo Serra and Sesso, {Howard D.} and Gianluca Severi and Hongbing Shen and Min Shen and Sanjay Shete and Kouya Shiraishi and Shu, {Xiao Ou} and Afshan Siddiq and Luis Sierrasesumaga and Sabina Sierri and Sihoe, {Alan Dart Loon} and Silverman, {Debra T.} and Matthias Simon and Southey, {Melissa C.} and Logan Spector and Margaret Spitz and Meir Stampfer and Par Stattin and Stern, {Mariana C.} and Stevens, {Victoria L.} and Stolzenberg-Solomon, {Rachael Z.} and Stram, {Daniel O.} and Strom, {Sara S.} and Su, {Wu Chou} and Malin Sund and Sung, {Sook Whan} and Anthony Swerdlow and Wen Tan and Hideo Tanaka and Wei Tang and Tang, {Ze Zhang} and Adonina Tardon and Evelyn Tay and Taylor, {Philip R.} and Yao Tettey and Thomas, {David M.} and Roberto Tirabosco and Anne Tjonneland and Tobias, {Geoffrey S.} and Toro, {Jorge R.} and Travis, {Ruth C.} and Dimitrios Trichopoulos and Rebecca Troisi and Ann Truelove and Tsai, {Ying Huang} and Tucker, {Margaret A.} and Rosario Tumino and {Van Den Berg}, David and {Van Den Eeden}, {Stephen K.} and Roel Vermeulen and Paolo Vineis and Kala Visvanathan and Ulla Vogel and Chaoyu Wang and Chengfeng Wang and Junwen Wang and Wang, {Sophia S.} and Elisabete Weiderpass and Weinstein, {Stephanie J.} and Nicolas Wentzensen and William Wheeler and Emily White and Wiencke, {John K.} and Alicja Wolk and Wolpin, {Brian M.} and Wong, {Maria Pik} and Margaret Wrensch and Chen Wu and Tangchun Wu and Xifeng Wu and Wu, {Yi Long} and Wunder, {Jay S.} and Xiang, {Yong Bing} and Jun Xu and Yang, {Hannah P.} and Yang, {Pan Chyr} and Yasushi Yatabe and Yuanqing Ye and Yeboah, {Edward D.} and Zhihua Yin and Chen Ying and Yu, {Chong Jen} and Kai Yu and Yuan, {Jian Min} and Zanetti, {Krista A.} and Anne Zeleniuch-Jacquotte and Wei Zheng and Baosen Zhou and Lisa Mirabello and Savage, {Sharon A.} and Peter Kraft and Chanock, {Stephen J.} and Meredith Yeager and Landi, {Maria Terese} and Jianxin Shi and Nilanjan Chatterjee and Amundadottir, {Laufey T.}",
year = "2014",
month = "11",
day = "15",
doi = "10.1093/hmg/ddu363",
language = "English (US)",
volume = "23",
pages = "6616--6633",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "24",

}

TY - JOUR

T1 - Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

AU - Wang, Zhaoming

AU - Zhu, Bin

AU - Zhang, Mingfeng

AU - Parikh, Hemang

AU - Jia, Jinping

AU - Chung, Charles C.

AU - Sampson, Joshua N.

AU - Hoskins, Jason W.

AU - Hutchinson, Amy

AU - Burdette, Laurie

AU - Ibrahim, Abdisamad

AU - Hautman, Christopher

AU - Raj, Preethi S.

AU - Abnet, Christian C.

AU - Adjei, Andrew A.

AU - Ahlbom, Anders

AU - Albanes, Demetrius

AU - Allen, Naomi E.

AU - Ambrosone, Christine B.

AU - Aldrich, Melinda

AU - Amiano, Pilar

AU - Amos, Christopher

AU - Andersson, Ulrika

AU - Gerald Andriole, G. A.

AU - Andrulis, Irene L.

AU - Arici, Cecilia

AU - Arslan, Alan A.

AU - Austin, Melissa A.

AU - Baris, Dalsu

AU - Barkauskas, Donald A.

AU - Bassig, Bryan A.

AU - Freeman, Laura E Beane

AU - Berg, Christine D.

AU - Berndt, Sonja I.

AU - Bertazzi, Pier Alberto

AU - Biritwum, Richard B.

AU - Black, Amanda

AU - Blot, William

AU - Boeing, Heiner

AU - Boffetta, Paolo

AU - Bolton, Kelly

AU - Boutron-Ruault, Marie Christine

AU - Bracci, Paige M.

AU - Brennan, Paul

AU - Brinton, Louise A.

AU - Brotzman, Michelle

AU - Bueno-de-Mesquita, H. Bas

AU - Buring, Julie E.

AU - Butler, Mary Ann

AU - Cai, Qiuyin

AU - Cancel-Tassin, Geraldine

AU - Canzian, Federico

AU - Cao, Guangwen

AU - Caporaso, Neil E.

AU - Carrato, Alfredo

AU - Carreon, Tania

AU - Carta, Angela

AU - Chang, Gee Chen

AU - Chang, I. Shou

AU - Chang-Claude, Jenny

AU - Che, Xu

AU - Chen, Chien Jen

AU - Chen, Chih Yi

AU - Chen, Chung Hsing

AU - Chen, Constance

AU - Chen, Kuan Yu

AU - Chen, Yuh Min

AU - Chokkalingam, Anand P.

AU - Chu, Lisa W.

AU - Clavel-Chapelon, Francoise

AU - Colditz, Graham A.

AU - Colt, Joanne S.

AU - Conti, David

AU - Cook, Michael B.

AU - Cortessis, Victoria K.

AU - Crawford, E. David

AU - Cussenot, Olivier

AU - Davis, Faith G.

AU - De Vivo, Immaculata

AU - Deng, Xiang

AU - Ding, Ti

AU - Dinney, Colin P.

AU - Di Stefano, Anna Luisa

AU - Diver, W. Ryan

AU - Duell, Eric J.

AU - Elena, Joanne W.

AU - Fan, Jin Hu

AU - Feigelson, Heather Spencer

AU - Feychting, Maria

AU - Figueroa, Jonine D.

AU - Flanagan, Adrienne M.

AU - Fraumeni, Joseph F.

AU - Freedman, Neal D.

AU - Fridley, Brooke L.

AU - Fuchs, Charles S.

AU - Gago-Dominguez, Manuela

AU - Gallinger, Steven

AU - Gao, Yu Tang

AU - Gapstur, Susan M.

AU - Garcia-Closas, Montserrat

AU - Garcia-Closas, Reina

AU - Gastier-Foster, Julie M.

AU - Gaziano, J. Michael

AU - Gerhard, Daniela S.

AU - Giffen, Carol A.

AU - Giles, Graham G.

AU - Gillanders, Elizabeth M.

AU - Giovannucci, Edward L.

AU - Goggins, Michael

AU - Gokgoz, Nalan

AU - Goldstein, Alisa M.

AU - Gonzalez, Carlos

AU - Gorlick, Richard

AU - Greene, Mark H.

AU - Gross, Myron

AU - Grossman, H. Barton

AU - Grubb, Robert

AU - Gu, Jian

AU - Guan, Peng

AU - Haiman, Christopher A.

AU - Hallmans, Goran

AU - Hankinson, Susan E.

AU - Harris, Curtis C.

AU - Hartge, Patricia

AU - Hattinger, Claudia

AU - Hayes, Richard B.

AU - He, Qincheng

AU - Helman, Lee

AU - Henderson, Brian E.

AU - Henriksson, Roger

AU - Hoffman-Bolton, Judith

AU - Hohensee, Chancellor

AU - Holly, Elizabeth A.

AU - Hong, Yun Chul

AU - Hoover, Robert N.

AU - Dean Hosgood, H.

AU - Hsiao, Chin Fu

AU - Hsing, Ann W.

AU - Hsiung, Chao Agnes

AU - Hu, Nan

AU - Hu, Wei

AU - Hu, Zhibin

AU - Huang, Ming Shyan

AU - Hunter, David J.

AU - Inskip, Peter D.

AU - Ito, Hidemi

AU - Jacobs, Eric J.

AU - Jacobs, Kevin B.

AU - Jenab, Mazda

AU - Ji, Bu Tian

AU - Johansen, Christoffer

AU - Johansson, Mattias

AU - Johnson, Alison

AU - Kaaks, Rudolf

AU - Kamat, Ashish M.

AU - Kamineni, Aruna

AU - Karagas, Margaret

AU - Khanna, Chand

AU - Khaw, Kay Tee

AU - Kim, Christopher

AU - Kim, In Sam

AU - Kim, Jin Hee

AU - Kim, Yeul Hong

AU - Kim, Young Chul

AU - Kim, Young Tae

AU - Kang, Chang Hyun

AU - Jung, Yoo Jin

AU - Kitahara, Cari M.

AU - Klein, Alison P.

AU - Klein, Robert

AU - Kogevinas, Manolis

AU - Koh, Woon Puay

AU - Kohno, Takashi

AU - Kolonel, Laurence N.

AU - Kooperberg, Charles

AU - Kratz, Christian P.

AU - Krogh, Vittorio

AU - Kunitoh, Hideo

AU - Kurtz, Robert C.

AU - Kurucu, Nilgun

AU - Lan, Qing

AU - Lathrop, Mark

AU - Lau, Ching C.

AU - Lecanda, Fernando

AU - Lee, Kyoung Mu

AU - Lee, Maxwell P.

AU - Marchand, Loic Le

AU - Lerner, Seth P.

AU - Li, Donghui

AU - Liao, Linda M.

AU - Lim, Wei Yen

AU - Lin, Dongxin

AU - Lin, Jie

AU - Lindstrom, Sara

AU - Linet, Martha S.

AU - Lissowska, Jolanta

AU - Liu, Jianjun

AU - Ljungberg, Börje

AU - Lloreta, Josep

AU - Lu, Daru

AU - Ma, Jing

AU - Malats, Nuria

AU - Mannisto, Satu

AU - Marina, Neyssa

AU - Mastrangelo, Giuseppe

AU - Matsuo, Keitaro

AU - McGlynn, Katherine A.

AU - McKean-Cowdin, Roberta

AU - McNeil, Lorna H.

AU - Mc Williams, Robert R

AU - Melin, Beatrice S.

AU - Meltzer, Paul S.

AU - Mensah, James E.

AU - Miao, Xiaoping

AU - Michaud, Dominique S.

AU - Mondul, Alison M.

AU - Moore, Lee E.

AU - Muir, Kenneth

AU - Niwa, Shelley

AU - Olson, Sara H.

AU - Orr, Nick

AU - Panico, Salvatore

AU - Park, Jae Yong

AU - Patel, Alpa V.

AU - Patino-Garcia, Ana

AU - Pavanello, Sofia

AU - Peeters, Petra H M

AU - Peplonska, Beata

AU - Peters, Ulrike

AU - Petersen, Gloria M

AU - Picci, Piero

AU - Pike, Malcolm C.

AU - Porru, Stefano

AU - Prescott, Jennifer

AU - Pu, Xia

AU - Purdue, Mark P.

AU - Qiao, You Lin

AU - Rajaraman, Preetha

AU - Riboli, Elio

AU - Risch, Harvey A.

AU - Rodabough, Rebecca J.

AU - Rothman, Nathaniel

AU - Ruder, Avima M.

AU - Ryu, Jeong Seon

AU - Sanson, Marc

AU - Schned, Alan

AU - Schumacher, Fredrick R.

AU - Schwartz, Ann G.

AU - Schwartz, Kendra L.

AU - Schwenn, Molly

AU - Scotlandi, Katia

AU - Seow, Adeline

AU - Serra, Consol

AU - Serra, Massimo

AU - Sesso, Howard D.

AU - Severi, Gianluca

AU - Shen, Hongbing

AU - Shen, Min

AU - Shete, Sanjay

AU - Shiraishi, Kouya

AU - Shu, Xiao Ou

AU - Siddiq, Afshan

AU - Sierrasesumaga, Luis

AU - Sierri, Sabina

AU - Sihoe, Alan Dart Loon

AU - Silverman, Debra T.

AU - Simon, Matthias

AU - Southey, Melissa C.

AU - Spector, Logan

AU - Spitz, Margaret

AU - Stampfer, Meir

AU - Stattin, Par

AU - Stern, Mariana C.

AU - Stevens, Victoria L.

AU - Stolzenberg-Solomon, Rachael Z.

AU - Stram, Daniel O.

AU - Strom, Sara S.

AU - Su, Wu Chou

AU - Sund, Malin

AU - Sung, Sook Whan

AU - Swerdlow, Anthony

AU - Tan, Wen

AU - Tanaka, Hideo

AU - Tang, Wei

AU - Tang, Ze Zhang

AU - Tardon, Adonina

AU - Tay, Evelyn

AU - Taylor, Philip R.

AU - Tettey, Yao

AU - Thomas, David M.

AU - Tirabosco, Roberto

AU - Tjonneland, Anne

AU - Tobias, Geoffrey S.

AU - Toro, Jorge R.

AU - Travis, Ruth C.

AU - Trichopoulos, Dimitrios

AU - Troisi, Rebecca

AU - Truelove, Ann

AU - Tsai, Ying Huang

AU - Tucker, Margaret A.

AU - Tumino, Rosario

AU - Van Den Berg, David

AU - Van Den Eeden, Stephen K.

AU - Vermeulen, Roel

AU - Vineis, Paolo

AU - Visvanathan, Kala

AU - Vogel, Ulla

AU - Wang, Chaoyu

AU - Wang, Chengfeng

AU - Wang, Junwen

AU - Wang, Sophia S.

AU - Weiderpass, Elisabete

AU - Weinstein, Stephanie J.

AU - Wentzensen, Nicolas

AU - Wheeler, William

AU - White, Emily

AU - Wiencke, John K.

AU - Wolk, Alicja

AU - Wolpin, Brian M.

AU - Wong, Maria Pik

AU - Wrensch, Margaret

AU - Wu, Chen

AU - Wu, Tangchun

AU - Wu, Xifeng

AU - Wu, Yi Long

AU - Wunder, Jay S.

AU - Xiang, Yong Bing

AU - Xu, Jun

AU - Yang, Hannah P.

AU - Yang, Pan Chyr

AU - Yatabe, Yasushi

AU - Ye, Yuanqing

AU - Yeboah, Edward D.

AU - Yin, Zhihua

AU - Ying, Chen

AU - Yu, Chong Jen

AU - Yu, Kai

AU - Yuan, Jian Min

AU - Zanetti, Krista A.

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Zhou, Baosen

AU - Mirabello, Lisa

AU - Savage, Sharon A.

AU - Kraft, Peter

AU - Chanock, Stephen J.

AU - Yeager, Meredith

AU - Landi, Maria Terese

AU - Shi, Jianxin

AU - Chatterjee, Nilanjan

AU - Amundadottir, Laufey T.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - 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 CLPTM1Lgene(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.

AB - 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 CLPTM1Lgene(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.

UR - http://www.scopus.com/inward/record.url?scp=84938138638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938138638&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu363

DO - 10.1093/hmg/ddu363

M3 - Article

C2 - 25027329

AN - SCOPUS:84938138638

VL - 23

SP - 6616

EP - 6633

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 24

ER -