@article{3163836,
    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",
    author = "Wang, Zhaoming and Zhu, Bin and Zhang, Mingfeng and Parikh, Hemang and and Jia, Jinping and Chung, Charles C. and Sampson, Joshua N. and Hoskins, and Jason W. and Hutchinson, Amy and Burdette, Laurie and Ibrahim, Abdisamad and and Hautman, Christopher and Raj, Preethi S. and Abnet, Christian C. and and Adjei, Andrew A. and Ahlbom, Anders and Albanes, Demetrius and Allen, and Naomi E. and Ambrosone, Christine B. and Aldrich, Melinda and Amiano, and Pilar and Amos, Christopher and Andersson, Ulrika and Andriole, Jr., and Gerald and Andrulis, Irene L. and Arici, Cecilia and Arslan, Alan A. and and Austin, Melissa A. and Baris, Dalsu and Barkauskas, Donald A. and and Bassig, Bryan A. and Freeman, Laura E. Beane and Berg, Christine D. and and Berndt, Sonja I. and Bertazzi, Pier Alberto and Biritwum, Richard B. and and Black, Amanda and Blot, William and Boeing, Heiner and Boffetta, Paolo and and Bolton, Kelly and Boutron-Ruault, Marie-Christine and Bracci, Paige and M. and Brennan, Paul and Brinton, Louise A. and Brotzman, Michelle and and Bueno-de-Mesquita, H. Bas and Buring, Julie E. and Butler, Mary Ann and and Cai, Qiuyin and Cancel-Tassin, Geraldine and Canzian, Federico and Cao, and Guangwen and Caporaso, Neil E. and Carrato, Alfredo and Carreon, Tania and and Carta, Angela and Chang, Gee-Chen and Chang, I-Shou and and Chang-Claude, Jenny and Che, Xu and Chen, Chien-Jen and Chen, Chih-Yi and and Chen, Chung-Hsing and Chen, Constance and Chen, Kuan-Yu and Chen, and Yuh-Min and Chokkalingam, Anand P. and Chu, Lisa W. and Clavel-Chapelon, and Francoise and Colditz, Graham A. and Colt, Joanne S. and Conti, David and and Cook, Michael B. and Cortessis, Victoria K. and Crawford, E. David and and Cussenot, Olivier and Davis, Faith G. and De Vivo, Immaculata and and Deng, Xiang and Ding, Ti and Dinney, Colin P. and Di Stefano, Anna Luisa and and Diver, W. Ryan and Duell, Eric J. and Elena, Joanne W. and Fan, and Jin-Hu and Feigelson, Heather Spencer and Feychting, Maria and Figueroa, and Jonine D. and Flanagan, Adrienne M. and Fraumeni, Jr., Joseph F. and and Freedman, Neal D. and Fridley, Brooke L. and Fuchs, Charles S. and and Gago-Dominguez, Manuela and Gallinger, Steven and Gao, Yu-Tang and and Gapstur, Susan M. and Garcia-Closas, Montserrat and Garcia-Closas, Reina and and Gastier-Foster, Julie M. and Gaziano, J. Michael and Gerhard, and Daniela S. and Giffen, Carol A. and Giles, Graham G. and Gillanders, and Elizabeth M. and Giovannucci, Edward L. and Goggins, Michael and Gokgoz, and Nalan and Goldstein, Alisa M. and Gonzalez, Carlos and Gorlick, Richard and and Greene, Mark H. and Gross, Myron and Grossman, H. Barton and Grubb, and III, Robert and Gu, Jian and Guan, Peng and Haiman, Christopher A. and and Hallmans, Goran and Hankinson, Susan E. and Harris, Curtis C. and and Hartge, Patricia and Hattinger, Claudia and Hayes, Richard B. and He, and Qincheng and Helman, Lee and Henderson, Brian E. and Henriksson, Roger and and Hoffman-Bolton, Judith and Hohensee, Chancellor and Holly, Elizabeth and A. and Hong, Yun-Chul and Hoover, Robert N. and Hosgood, H. Dean and and Hsiao, Chin-Fu and Hsing, Ann W. and Hsiung, Chao Agnes and Hu, Nan and and Hu, Wei and Hu, Zhibin and Huang, Ming-Shyan and Hunter, David J. and and Inskip, Peter D. and Ito, Hidemi and Jacobs, Eric J. and Jacobs, Kevin and B. and Jenab, Mazda and Ji, Bu-Tian and Johansen, Christoffer and and Johansson, Mattias and Johnson, Alison and Kaaks, Rudolf and Kamat, and Ashish M. and Kamineni, Aruna and Karagas, Margaret and Khanna, Chand and and Khaw, Kay-Tee and Kim, Christopher and Kim, In-Sam and Kim, Jin Hee and and Kim, Yeul Hong and Kim, Young-Chul and Kim, Young Tae and Kang, and Chang Hyun and Jung, Yoo Jin and Kitahara, Cari M. and Klein, Alison P. and and Klein, Robert and Kogevinas, Manolis and Koh, Woon-Puay and Kohno, and Takashi and Kolonel, Laurence N. and Kooperberg, Charles and Kratz, and Christian P. and Krogh, Vittorio and Kunitoh, Hideo and Kurtz, Robert C. and and Kurucu, Nilgun and Lan, Qing and Lathrop, Mark and Lau, Ching C. and and Lecanda, Fernando and Lee, Kyoung-Mu and Lee, Maxwell P. and Le and Marchand, Loic and Lerner, Seth P. and Li, Donghui and Liao, Linda M. and and Lim, Wei-Yen and Lin, Dongxin and Lin, Jie and Lindstrom, Sara and and Linet, Martha S. and Lissowska, Jolanta and Liu, Jianjun and Ljungberg, and Boerje and Lloreta, Josep and Lu, Daru and Ma, Jing and Malats, Nuria and and Mannisto, Satu and Marina, Neyssa and Mastrangelo, Giuseppe and and Matsuo, Keitaro and McGlynn, Katherine A. and McKean-Cowdin, Roberta and and McNeill, Lorna H. and McWilliams, Robert R. and Melin, Beatrice S. and and Meltzer, Paul S. and Mensah, James E. and Miao, Xiaoping and Michaud, and Dominique S. and Mondul, Alison M. and Moore, Lee E. and Muir, Kenneth and and Niwa, Shelley and Olson, Sara H. and Orr, Nick and Panico, Salvatore and and Park, Jae Yong and Patel, Alpa V. and Patino-Garcia, Ana and and Pavanello, Sofia and Peeters, Petra H. M. and Peplonska, Beata and and Peters, Ulrike and Petersen, Gloria M. and Picci, Piero and Pike, and Malcolm C. and Porru, Stefano and Prescott, Jennifer and Pu, Xia and and Purdue, Mark P. and Qiao, You-Lin and Rajaraman, Preetha and Riboli, and Elio and Risch, Harvey A. and Rodabough, Rebecca J. and Rothman, and Nathaniel and Ruder, Avima M. and Ryu, Jeong-Seon and Sanson, Marc and and Schned, Alan and Schumacher, Fredrick R. and Schwartz, Ann G. and and Schwartz, Kendra L. and Schwenn, Molly and Scotlandi, Katia and Seow, and Adeline and Serra, Consol and Serra, Massimo and Sesso, Howard D. and and Severi, Gianluca and Shen, Hongbing and Shen, Min and Shete, Sanjay and and Shiraishi, Kouya and Shu, Xiao-Ou and Siddiq, Afshan and Sierrasesumaga, and Luis and Sierri, Sabina and Sihoe, Alan Dart Loon and Silverman, Debra and T. and Simon, Matthias and Southey, Melissa C. and Spector, Logan and and Spitz, Margaret and Stampfer, Meir and Stattin, Par and Stern, Mariana and C. and Stevens, Victoria L. and Stolzenberg-Solomon, Rachael Z. and and Stram, Daniel O. and Strom, Sara S. and Su, Wu-Chou and Sund, Malin and and Sung, Sook Whan and Swerdlow, Anthony and Tan, Wen and Tanaka, Hideo and and Tang, Wei and Tang, Ze-Zhang and Tardon, Adonina and Tay, Evelyn and and Taylor, Philip R. and Tettey, Yao and Thomas, David M. and Tirabosco, and Roberto and Tjonneland, Anne and Tobias, Geoffrey S. and Toro, Jorge R. and and Travis, Ruth C. and Trichopoulos, Dimitrios and Troisi, Rebecca and and Truelove, Ann and Tsai, Ying-Huang and Tucker, Margaret A. and Tumino, and Rosario and Van Den Berg, David and Van Den Eeden, Stephen K. and and Vermeulen, Roel and Vineis, Paolo and Visvanathan, Kala and Vogel, Ulla and and Wang, Chaoyu and Wang, Chengfeng and Wang, Junwen and Wang, Sophia and S. and Weiderpass, Elisabete and Weinstein, Stephanie J. and Wentzensen, and Nicolas and Wheeler, William and White, Emily and Wiencke, John K. and and Wolk, Alicja and Wolpin, Brian M. and Wong, Maria Pik and Wrensch, and Margaret and Wu, Chen and Wu, Tangchun and Wu, Xifeng and Wu, Yi-Long and and Wunder, Jay S. and Xiang, Yong-Bing and Xu, Jun and Yang, Hannah P. and and Yang, Pan-Chyr and Yatabe, Yasushi and Ye, Yuanqing and Yeboah, and Edward D. and Yin, Zhihua and Ying, Chen and Yu, Chong-Jen and Yu, Kai and and Yuan, Jian-Min and Zanetti, Krista A. and Zeleniuch-Jacquotte, Anne and and Zheng, Wei and Zhou, Baosen and Mirabello, Lisa and Savage, Sharon and A. and Kraft, Peter and Chanock, Stephen J. and Yeager, Meredith and and Landi, Maria Terese and Shi, Jianxin and Chatterjee, Nilanjan and and Amundadottir, Laufey T.",
    journal = "Human Molecular Genetics",
    year = "2014",
    volume = "23",
    number = "24",
    pages = "6616-6633",
    publisher = "Oxford University Press",
    issn = "0964-6906, 1460-2083",
    doi = "10.1093/hmg/ddu363",
    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 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."
}