Format

Send to

Choose Destination
See comment in PubMed Commons below
Hum Mol Genet. 2014 Dec 15;23(24):6616-33. doi: 10.1093/hmg/ddu363. Epub 2014 Jul 15.

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 Z1, Zhu B2, Zhang M2, Parikh H2, Jia J2, Chung CC1, Sampson JN2, Hoskins JW2, Hutchinson A1, Burdette L1, Ibrahim A2, Hautman C1, Raj PS2, Abnet CC2, Adjei AA3, Ahlbom A4, Albanes D2, Allen NE5, Ambrosone CB6, Aldrich M7, Amiano P8, Amos C9, Andersson U10, Andriole G Jr11, Andrulis IL12, Arici C13, Arslan AA14, Austin MA15, Baris D2, Barkauskas DA16, Bassig BA17, Beane Freeman LE2, Berg CD18, Berndt SI2, Bertazzi PA19, Biritwum RB3, Black A2, Blot W20, Boeing H21, Boffetta P22, Bolton K23, Boutron-Ruault MC24, Bracci PM25, Brennan P26, Brinton LA2, Brotzman M27, Bueno-de-Mesquita HB28, Buring JE29, Butler MA30, Cai Q7, Cancel-Tassin G31, Canzian F32, Cao G33, Caporaso NE2, Carrato A34, Carreon T30, Carta A12, Chang GC35, Chang IS36, Chang-Claude J32, Che X37, Chen CJ38, Chen CY39, Chen CH36, Chen C40, Chen KY41, Chen YM42, Chokkalingam AP43, Chu LW44, Clavel-Chapelon F45, Colditz GA46, Colt JS2, Conti D16, Cook MB2, Cortessis VK16, Crawford ED47, Cussenot O48, Davis FG49, De Vivo I50, Deng X1, Ding T51, Dinney CP52, Di Stefano AL53, Diver WR54, Duell EJ55, Elena JW56, Fan JH57, Feigelson HS58, Feychting M4, Figueroa JD2, Flanagan AM59, Fraumeni JF Jr2, Freedman ND2, Fridley BL60, Fuchs CS61, Gago-Dominguez M62, Gallinger S63, Gao YT64, Gapstur SM54, Garcia-Closas M65, Garcia-Closas R66, Gastier-Foster JM67, Gaziano JM68, Gerhard DS69, Giffen CA70, Giles GG71, Gillanders EM72, Giovannucci EL73, Goggins M74, Gokgoz N75, Goldstein AM2, Gonzalez C76, Gorlick R77, Greene MH2, Gross M78, Grossman HB52, Grubb R 3rd79, Gu J80, Guan P81, Haiman CA82, Hallmans G83, Hankinson SE84, Harris CC85, Hartge P2, Hattinger C86, Hayes RB87, He Q81, Helman L88, Henderson BE82, Henriksson R10, Hoffman-Bolton J89, Hohensee C90, Holly EA25, Hong YC91, Hoover RN2, Hosgood HD 3rd92, Hsiao CF93, Hsing AW94, Hsiung CA95, Hu N2, Hu W2, Hu Z96, Huang MS41, Hunter DJ97, Inskip PD2, Ito H98, Jacobs EJ54, Jacobs KB99, Jenab M26, Ji BT2, Johansen C100, Johansson M101, Johnson A102, Kaaks R32, Kamat AM52, Kamineni A103, Karagas M9, Khanna C88, Khaw KT104, Kim C2, Kim IS105, Kim JH106, Kim YH107, Kim YC108, Kim YT109, Kang CH109, Jung YJ109, Kitahara CM2, Klein AP110, Klein R111, Kogevinas M112, Koh WP113, Kohno T114, Kolonel LN115, Kooperberg C90, Kratz CP2, Krogh V116, Kunitoh H117, Kurtz RC111, Kurucu N118, Lan Q2, Lathrop M119, Lau CC120, Lecanda F121, Lee KM122, Lee MP88, Le Marchand L115, Lerner SP123, Li D124, Liao LM2, Lim WY125, Lin D126, Lin J80, Lindstrom S40, Linet MS2, Lissowska J127, Liu J128, Ljungberg B129, Lloreta J130, Lu D131, Ma J132, Malats N133, Mannisto S134, Marina N135, Mastrangelo G136, Matsuo K137, McGlynn KA2, McKean-Cowdin R80, McNeill LH138, McWilliams RR139, Melin BS10, Meltzer PS88, Mensah JE3, Miao X140, Michaud DS141, Mondul AM2, Moore LE2, Muir K142, Niwa S27, Olson SH143, Orr N144, Panico S145, Park JY146, Patel AV54, Patino-Garcia A121, Pavanello S136, Peeters PH147, Peplonska B148, Peters U90, Petersen GM139, Picci P86, Pike MC149, Porru S13, Prescott J50, Pu X80, Purdue MP2, Qiao YL150, Rajaraman P2, Riboli E151, Risch HA152, Rodabough RJ90, Rothman N2, Ruder AM30, Ryu JS153, Sanson M53, Schned A9, Schumacher FR82, Schwartz AG154, Schwartz KL155, Schwenn M156, Scotlandi K86, Seow A125, Serra C157, Serra M86, Sesso HD29, Severi G71, Shen H96, Shen M2, Shete S158, Shiraishi K114, Shu XO7, Siddiq A159, Sierrasesumaga L121, Sierri S160, Loon Sihoe AD161, Silverman DT2, Simon M162, Southey MC163, Spector L164, Spitz M165, Stampfer M132, Stattin P129, Stern MC82, Stevens VL54, Stolzenberg-Solomon RZ2, Stram DO82, Strom SS166, Su WC167, Sund M168, Sung SW169, Swerdlow A170, Tan W126, Tanaka H98, Tang W2, Tang ZZ51, Tardon A171, Tay E3, Taylor PR2, Tettey Y3, Thomas DM172, Tirabosco R173, Tjonneland A174, Tobias GS2, Toro JR2, Travis RC5, Trichopoulos D175, Troisi R2, Truelove A27, Tsai YH176, Tucker MA2, Tumino R177, Van Den Berg D82, Van Den Eeden SK178, Vermeulen R179, Vineis P180, Visvanathan K89, Vogel U181, Wang C2, Wang C37, Wang J182, Wang SS183, Weiderpass E184, Weinstein SJ2, Wentzensen N2, Wheeler W70, White E90, Wiencke JK185, Wolk A186, Wolpin BM61, Wong MP187, Wrensch M185, Wu C126, Wu T136, Wu X80, Wu YL188, Wunder JS11, Xiang YB64, Xu J189, Yang HP2, Yang PC41, Yatabe Y190, Ye Y80, Yeboah ED3, Yin Z81, Ying C125, Yu CJ167, Yu K2, Yuan JM191, Zanetti KA56, Zeleniuch-Jacquotte A192, Zheng W7, Zhou B81, Mirabello L2, Savage SA2, Kraft P193, Chanock SJ1, Yeager M1, Landi MT2, Shi J2, Chatterjee N2, Amundadottir LT194.

Author information

1
Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
2
Division of Cancer Epidemiology and Genetics.
3
Korle Bu Teaching Hospital, PO BOX 77, Accra, Ghana, University of Ghana Medical School, PO Box 4236, Accra, Ghana.
4
Unit of Epidemiology, Institute of Environmental Medicine.
5
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.
6
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
7
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
8
Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain, CIBERESP, CIBER Epidemiologia y Salud Publica, Madrid, Spain.
9
Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
10
Department of Radiation Sciences, Oncology.
11
Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, USA.
12
Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, ON, Canada.
13
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy.
14
Department of Obstetrics and Gynecology and Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA.
15
Department of Epidemiology, University of Washington, Seattle, WA, USA.
16
Department of Preventive Medicine, Biostatistics Division, Keck School of Medicine and.
17
Division of Cancer Epidemiology and Genetics, Division of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
18
Division of Cancer Prevention.
19
Department of Clinical Sciences and Community Health, University of Milan, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Policlinico Hospital, Milan, Italy.
20
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, International Epidemiology Institute, Rockville, MD, USA.
21
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.
22
Institute for Translational Epidemiology, Hematology and Medical Oncology, Mount Sinai Hospital School of Medicine, New York, NY, USA.
23
Division of Cancer Epidemiology and Genetics, Department of Oncology, University of Cambridge, Cambridge CB2 2RE, UK.
24
Institut National de la Sante et de la Recherche Medicale (INSERM) and Institut Gustave Roussy, Villejuif, France.
25
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
26
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
27
Westat, Rockville, MD, USA.
28
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands.
29
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
30
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH, USA.
31
CeRePP, Paris, France, UPMC Univ Paris 06, GRC n°5, ONCOTYPE-URO, Paris, France.
32
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
33
Department of Epidemiology, Second Military Medical University, Shanghai, China.
34
Medical Oncology Department, Hospital Ramón y Cajal, Madrid, Spain.
35
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
36
National Institute of Cancer Research.
37
Department of Abdominal Surgery and.
38
Genomics Research Center, Academia Sinica, Taipei, Taiwan, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
39
Cancer Center, China Medical University Hospital, Taipei, Taiwan.
40
Program in Molecular and Genetic Epidemiology.
41
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
42
Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine and Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, College of Medical Science and Technology, Taipei Medical University, Taiwan.
43
School of Public Health, University of California, Berkeley, CA, USA.
44
Cancer Prevention Institute of California, Fremont, CA, USA.
45
Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
46
Washington University School of Medicine, St Louis, MO, USA.
47
Urologic Oncology, University of Colorado, Aurora, CO, USA.
48
CeRePP, Paris, France, AP-HP, Department of Urology, Tenon Hospital, GHU-Est, Paris, France, UPMC Univ Paris 06, GRC n°5, ONCOTYPE-URO, Paris, France.
49
Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, AB, Canada T6G 2R3.
50
Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
51
Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China.
52
Department of Urology.
53
Service de Neurologie Mazarin, GH Pitie-Salpetriere, APHP, and UMR 975 INSERM-UPMC, CRICM, Paris, France.
54
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
55
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
56
Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, Bethesda, MD, USA.
57
Shanghai Cancer Institute, Shanghai, People's Republic of China.
58
Institute for Health Research, Kaiser Permanente, Denver, CO, USA.
59
UCL Cancer Institute, Huntley Street, London WC1E 6BT, UK, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
60
Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
61
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, Channing Laboratory, Department of Medicine.
62
Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
63
Samuel Lunenfeld Research Institute and.
64
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotaong University School of Medicine, Shanghai, China.
65
Division of Cancer Epidemiology and Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
66
Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain.
67
Nationwide Children's Hospital, and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH, USA.
68
Division of Preventive Medicine, Department of Medicine and Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA, USA.
69
Office of Cancer Genomics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
70
Information Management Services Inc., Calverton, MD, USA.
71
Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
72
Division of Cancer Control and Population Sciences and.
73
Program in Molecular and Genetic Epidemiology, Department of Nutrition and.
74
Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
75
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
76
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
77
Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY, USA.
78
Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
79
Department of Urology, Washington University School of Medicine, St Louis, MO, USA.
80
Department of Epidemiology.
81
Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
82
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
83
Department of Public Health and Clinical Medicine/Nutritional Research.
84
Channing Laboratory, Department of Medicine.
85
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
86
Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
87
Division of Cancer Epidemiology and Genetics, Department of Population Health, New York University Langone Medical Center and Department of Environmental Medicine, New York University Langone Medical Center, New York University Cancer Institute, New York, NY, USA.
88
Center for Cancer Research and.
89
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
90
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
91
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea, Department of Preventive Medicine and.
92
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
93
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and Taiwan Lung Cancer Tissue/Specimen Information Resource Center, National Health Research Institutes, Zhunan, Taiwan.
94
Cancer Prevention Institute of California, Fremont, CA, USA, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
95
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and.
96
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
97
Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
98
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
99
Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Bioinformed, LLC, Gaithersburg, MD, USA.
100
Department of Oncology, Finsen Center, Rigshospitalet, Copenhagen, Denmark, Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark.
101
International Agency for Research on Cancer (IARC-WHO), Lyon, France, Department of Public Health and Clinical Medicine.
102
Vermont Cancer Registry, Burlington, VT, USA.
103
Group Health Research Institute, Seattle, WA, USA.
104
School of Clinical Medicine, University of Cambridge, UK.
105
Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
106
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
107
Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University Anam Hospital, Seoul, Republic of Korea, Department of Internal Medicine and Division of Brain and Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
108
Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea.
109
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
110
Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
111
Department of Medicine and.
112
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece.
113
Duke-NUS Graduate Medical School, Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
114
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
115
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
116
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
117
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan, Department of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.
118
Department of Pediatric Oncology, A.Y. Ankara Oncology Training and Research Hospital, Yenimahalle- Ankara, Turkey.
119
Centre National de Genotypage, IG/CEA, Evry Cedex, France, Centre d'Étude du Polymorphism Humain (CEPH), Paris, France.
120
Texas Children's Cancer and Hematology Centers.
121
Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain.
122
Department of Preventive Medicine and Department of Environmental Health, Korea National Open University, Seoul, Republic of Korea.
123
Scott Department of Urology and.
124
Department of Gastrointestinal Medical Oncology.
125
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
126
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
127
Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
128
Human Genetics Division, Genome Institute of Singapore, Singapore, School of Life Sciences, Anhui Medical University, Hefei, China.
129
Department of Surgical and Perioperative Sciences, Urology and Andrology and.
130
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
131
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
132
Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
133
Centro Nacional de Investigaciones Oncologicas, Melchor Fernández Almagro, 3, Madrid E-28029, Spain.
134
National Institute for Health and Welfare, Helsinki, Finland.
135
Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA.
136
Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy.
137
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan, Department of Preventive Medicine, Kyushu University Faculty of Medical Scicence, Fukuoka, Japan.
138
Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community-Engaged Translational Research, Duncan Family Institute and.
139
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
140
Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.
141
Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, RI, USA.
142
Health Sciences Research Institute, University of Warwick, Coventry, UK.
143
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
144
Complex Traits Genetics Team and.
145
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
146
Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
147
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Utrecht, The Netherlands, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
148
Nofer Institute of Occupational Medicine, Lodz, Poland.
149
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
150
Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
151
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
152
Yale School of Public Health, New Haven, CT, USA.
153
Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.
154
Karmanos Cancer Institute and Department of Oncology and.
155
Karmanos Cancer Institute and Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA.
156
Maine Cancer Registry, Augusta, ME, USA.
157
Centre for Research in Occupational Health, Universitat Pompeu Fabra, Barcelona, Spain, CIBER of Epidemiology and Public Health (CIBERESP).
158
Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA.
159
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
160
Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
161
Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China.
162
Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
163
Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia.
164
University of Minnesota, Minneapolis, MN, USA.
165
Dan L. Duncan Center, Baylor College of Medicine, Houston, TX, USA.
166
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
167
Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan.
168
Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden.
169
Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, South Korea.
170
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK, Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
171
Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
172
Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrew's Place, East Melbourne, VIC, Australia.
173
Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
174
Danish Cancer Society Research Center, Copenhagen, Denmark.
175
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
176
Department of Pulmonary Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
177
Cancer Registry Associazione Iblea Ricerca Epidemiologica, Onlus and Asp Ragusa, Ragusa Italy.
178
Kaiser Permanente Northern California, Oakland, CA, USA.
179
Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
180
Imperial College, London, UK, Human Genetics Foundation (HuGeF), Torino Italy.
181
National Research Centre for the Working Environment, Copenhagen, Denmark, National Food Institute, Technical University of Denmark, Soborg, Denmark.
182
Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
183
Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, CA, USA.
184
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Department of Research, Cancer Registry of Norway, Oslo, Norway, Department of Medical Epidemiology and Biostatistics and Samfundet Folkhälsan, Helsinki, Finland.
185
University of California San Francisco, San Francisco, CA, USA.
186
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
187
Department of Pathology and.
188
Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
189
School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
190
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital and.
191
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA and.
192
Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA.
193
Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
194
Division of Cancer Epidemiology and Genetics, amundadottirl@mail.nih.gov.

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.

PMID:
25027329
PMCID:
PMC4240198
DOI:
10.1093/hmg/ddu363
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center