Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

被引：507

作者：

Rafnar, Thorunn ^{[1
]}

Sulem, Patrick ^{[1
]}

Stacey, Simon N. ^{[1
]}

Geller, Frank ^{[1
]}

Gudmundsson, Julius ^{[1
]}

Sigurdsson, Asgeir ^{[1
]}

Jakobsdottir, Margret ^{[1
]}

Helgadottir, Hafdis ^{[1
]}

Thorlacius, Steinunn ^{[1
]}

Aben, Katja K. H. ^{[2
,3
,4
]}

Bloendal, Thorarinn ^{[1
]}

Thorgeirsson, Thorgeir E. ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Kristjansson, Kristleifur ^{[1
]}

Thorisdottir, Kristin ^{[5
]}

Ragnarsson, Rafn ^{[6
]}

Sigurgeirsson, Bardur ^{[5
]}

Skuladottir, Halla ^{[7
]}

Gudbjartsson, Tomas ^{[8
,9
]}

Isaksson, Helgi J. ^{[10
]}

Einarsson, Gudmundur V. ^{[11
]}

Benediktsdottir, Kristrun R. ^{[9
,10
]}

Agnarsson, Bjarni A. ^{[9
,10
]}

Olafsson, Karl ^{[12
]}

Salvarsdottir, Anna ^{[12
]}

Bjarnason, Hjordis ^{[1
]}

Asgeirsdottir, Margret ^{[1
]}

Kristinsson, Kari T. ^{[1
]}

Matthiasdottir, Sigurborg ^{[1
]}

Sveinsdottir, Steinunn G. ^{[13
]}

Polidoro, Silvia ^{[14
,15
]}

Hoeiom, Veronica ^{[16
]}

Botella-Estrada, Rafael ^{[17
]}

Hemminki, Kari ^{[18
]}

Rudnai, Peter ^{[19
]}

Bishop, D. Timothy ^{[20
]}

Campagna, Marcello ^{[21
]}

Kellen, Eliane ^{[22
,23
]}

Zeegers, Maurice P. ^{[24
,25
]}

de Verdier, Petra ^{[26
]}

Ferrer, Ana ^{[27
]}

Isla, Dolores ^{[27
]}

Vidal, Maria Jesus ^{[27
]}

Andres, Raquel ^{[27
]}

Saez, Berta ^{[28
]}

Juberias, Pablo ^{[29
]}

Banzo, Javier ^{[30
]}

Navarrete, Sebastian ^{[31
]}

Tres, Alejandro ^{[27
,32
]}

Kan, Donghui ^{[33
]}

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat, NL-6500 HB Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, HTA, NL-6500 HB Nijmegen, Netherlands

[5] Univ Iceland, Dept Dermatol, IS-101 Reykjavik, Iceland

[6] Lanspitali Univ Hosp, Dept Plast Surg, IS-101 Reykjavik, Iceland

[7] Lanspitali Univ Hosp, Dept Med Oncol, IS-101 Reykjavik, Iceland

[8] Lanspitali Univ Hosp, Dept Surg, IS-101 Reykjavik, Iceland

[9] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[10] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland

[11] Landspitali Univ Hosp, Dept Urol, IS-101 Reykjavik, Iceland

[12] Landspitali Univ Hosp, Dept Obstet & Gynecol, IS-101 Reykjavik, Iceland

[13] Clin Res Ctr, IS-110 Reykjavik, Iceland

[14] ISI Fdn, Inst Sci Interchange, I-10133 Turin, Italy

[15] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy

[16] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden

[17] Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain

[18] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany

[19] Natl Inst Environm Hlth, H-1450 Budapest, Hungary

[20] St James Univ Hosp, Epidemiol & Biostat Sect, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

[21] Univ Brescia, Dept Expt & Appl Med, Sect Occupat Med & Ind Hyg, I-25125 Brescia, Italy

[22] Catholic Univ Leuven, Dept Gen Practice, B-3000 Louvain, Belgium

[23] Katholieke Univ Leuven, Ctr Canc Prevent LUCK, B-3000 Louvain, Belgium

[24] Univ Birmingham, Unit Genet Epidemiol, Dept Publ Hlth & Epidemiol, Birmingham B15 2TT, W Midlands, England

[25] Maastricht Univ, Dept Complex Genet Cluster Genet & Cell Biol, Nutr & Toxicol Res Inst, NL-6200 MD Maastricht, Netherlands

[26] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden

[27] Univ Hosp, Div Med Oncol, Zaragoza 50009, Spain

[28] Hlth Sci Inst, Zaragoza 50009, Spain

[29] Univ Hosp, Div Dermatol, Zaragoza 50009, Spain

[30] Univ Hosp, Div Nucl Med, Zaragoza 50009, Spain

[31] Univ Hosp, Div Radiat Oncol, Zaragoza 50009, Spain

[32] Nanotechnol Inst Aragon, Hlth Sci Inst, Zaragoza 50009, Spain

[33] Northwestern Univ, Dept Urol, Feinberg Sch Med, Chicago, IL 60611 USA

[34] Ctr Environm Hlth, Cluj Napoca 400166, Romania

[35] State Hlth Inst, SK-97556 Banska Bystrica, Slovakia

[36] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands

[37] Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, NL-6500 HB Nijmegen, Netherlands

[38] Rijnstate Hosp, Dept Pulm Med, Arnhem, Netherlands

[39] Canisius Wilhelmina Hosp, Dept Pulm Dis, NL-6532 SZ Nijmegen, Netherlands

[40] Sahlgrens Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden

[41] Maastricht Univ, Dept Gen Practice, NL-6200 MD Maastricht, Netherlands

[42] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England

[43] St James Univ Hosp, Sect Expt Oncol, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

[44] Landspitali Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; BASAL-CELL CARCINOMA; PROSTATE-CANCER; LUNG-CANCER; TELOMERE LENGTH; BREAST-CANCER; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; COMMON VARIANTS; RISK-FACTOR;

D O I：

10.1038/ng.296

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma(1), we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

引用

页码：221 / 227

页数：7

共 30 条

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Benediktsdottir, Kristrun R. ;

Cazier, Jean-Baptiste ;

Sainz, Jesus ;

Jakobsdottir, Margret ;

Kostic, Jelena ;

Magnusdottir, Droplaug N. ;

Ghosh, Shyamali ;

Agnarsson, Kari ;

Birgisdottir, Birgitta ;

Le Roux, Louise ;

Olafsdottir, Adalheidur ;

Blondal, Thorarinn ;

Andresdottir, Margret ;

Gretarsdottir, Olafia Svandis ;

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Gudbjartsson, Daniel ;

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Geirsson, Gudmundur ;

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Healey, Catherine S. ;

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Meyer, Kerstin B. ;

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Kolonel, Laurence K. ;

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Field, Helen I. ;

Southey, Melissa C. ;

Severi, Gianluca ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Dearnaley, David P. ;

Muir, Kenneth R. ;

Smith, Charmaine ;

Bagnato, Melisa ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Gehr-Swain, Beatrice N. ;

Wilkinson, Rosemary A. ;

Cox, Angie ;

Lewis, Sarah ;

Brown, Paul M. ;

Jhavar, Sameer G. ;

Tymrakiewicz, Malgorzata ;

Lophatananon, Artitaya ;

Bryant, Sarah L. ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

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Woodhouse, Christopher J. ;

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Ogden, Chris ;

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Blackburn, EH ;

Shannon, KM .

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Sulem, Patrick ;

Stacey, Simon N. ;

Goldstein, Alisa M. ;

Rafnar, Thorunn ;

Sigurgeirsson, Bardur ;

Benediktsdottir, Kristrun R. ;

Thorisdottir, Kristin ;

Ragnarsson, Rafn ;

Sveinsdottir, Steinunn G. ;

Magnusson, Veronica ;

Lindblom, Annika ;

Kostulas, Konstantinos ;

Botella-Estrada, Rafael ;

Soriano, Virtudes ;

Juberias, Pablo ;

Grasa, Matilde ;

Saez, Berta ;

Andres, Raquel ;

Scherer, Dominique ;

Rudnai, Peter ;

Gurzau, Eugene ;

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Walters, G. Bragi ;

Thorleifsson, Gudmar ;

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Sulem, Patrick ;

Manolescu, Andrei ;

Amundadottir, Laufey T. ;

Gudbjartsson, Daniel ;

Helgason, Agnar ;

Rafnar, Thorunn ;

Bergthorsson, Jon T. ;

Agnarsson, Bjarni A. ;

Baker, Adam ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Jakobsdottir, Margret ;

Xu, Jianfeng ;

Blondal, Thorarinn ;

Kostic, Jelena ;

Sun, Jielin ;

Ghosh, Shyamali ;

Stacey, Simon N. ;

Mouy, Magali ;

Saemundsdottir, Jona ;

Backman, Valgerdur M. ;

Kristjansson, Kristleifur ;

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Partin, Alan W. ;

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Walsh, Patrick C. ;

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Graif, Theresa ;

Cashy, John ;

Ruiz-Echarri, Manuel ;

Wiley, Kathleen E. ;

Suarez, Brian K. ;

Witjes, J. Alfred ;

Frigge, Mike ;

Ober, Carole ;

Jonsson, Eirikur ;

Einarsson, Gudmundur V. ;

Mayordomo, Jose I. ;

Kiemeney, Lambertus A. ;

Isaacs, William B. ;

Catalona, William J. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Thorsteinsdottir, Unnur ;

Kong, Augustine .

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Haiman, Christopher A. ;

Le Marchand, Loic ;

Yamamato, Jennifer ;

Stram, Daniel O. ;

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← 1 2 3 →

共 30 条

[1] Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 [J].

Amos, Christopher I. ;

Wu, Xifeng ;

Broderick, Peter ;

Gorlov, Ivan P. ;

Gu, Jian ;

Eisen, Timothy ;

Dong, Qiong ;

Zhang, Qing ;

Gu, Xiangjun ;

Vijayakrishnan, Jayaram ;

Sullivan, Kate ;

Matakidou, Athena ;

Wang, Yufei ;

Mills, Gordon ;

Doheny, Kimberly ;

Tsai, Ya-Yu ;

Chen, Wei Vivien ;

Shete, Sanjay ;

Spitz, Margaret R. ;

Houlston, Richard S. .

NATURE GENETICS, 2008, 40 (05) :616-622

[2] A common variant associated with prostate cancer in European and African populations [J].

Amundadottir, Laufey T. ;

Sulem, Patrick ;

Gudmundsson, Julius ;

Helgason, Agnar ;

Baker, Adam ;

Agnarsson, Bjarni A. ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Cazier, Jean-Baptiste ;

Sainz, Jesus ;

Jakobsdottir, Margret ;

Kostic, Jelena ;

Magnusdottir, Droplaug N. ;

Ghosh, Shyamali ;

Agnarsson, Kari ;

Birgisdottir, Birgitta ;

Le Roux, Louise ;

Olafsdottir, Adalheidur ;

Blondal, Thorarinn ;

Andresdottir, Margret ;

Gretarsdottir, Olafia Svandis ;

Bergthorsson, Jon T. ;

Gudbjartsson, Daniel ;

Gylfason, Arnaldur ;

Thorleifsson, Gudmar ;

Manolescu, Andrei ;

Kristjansson, Kristleifur ;

Geirsson, Gudmundur ;

Isaksson, Helgi ;

Douglas, Julie ;

Johansson, Jan-Erik ;

Balter, Katarina ;

Wiklund, Fredrik ;

Montie, James E. ;

Yu, Xiaoying ;

Suarez, Brian K. ;

Ober, Carole ;

Cooney, Kathleen A. ;

Gronberg, Henrik ;

Catalona, William J. ;

Einarsson, Gudmundur V. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Kong, Augustine ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE GENETICS, 2006, 38 (06) :652-658

[3] Switching and signaling at the telomere [J].

Blackburn, EH .

CELL, 2001, 106 (06) :661-673

[4] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[5] Multiple newly identified loci associated with prostate cancer susceptibility [J].

Eeles, Rosalind A. ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Al Olama, Ali Amin ;

Guy, Michelle ;

Jugurnauth, Sarah K. ;

Mulholland, Shani ;

Leongamornlert, Daniel A. ;

Edwards, Stephen M. ;

Morrison, Jonathan ;

Field, Helen I. ;

Southey, Melissa C. ;

Severi, Gianluca ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Dearnaley, David P. ;

Muir, Kenneth R. ;

Smith, Charmaine ;

Bagnato, Melisa ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Gehr-Swain, Beatrice N. ;

Wilkinson, Rosemary A. ;

Cox, Angie ;

Lewis, Sarah ;

Brown, Paul M. ;

Jhavar, Sameer G. ;

Tymrakiewicz, Malgorzata ;

Lophatananon, Artitaya ;

Bryant, Sarah L. ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Fisher, Cyril ;

Jamieson, Charles ;

Cooper, Colin S. ;

English, Dallas R. ;

Hopper, John L. ;

Neal, David E. ;

Easton, Douglas F. .

NATURE GENETICS, 2008, 40 (03) :316-321

[6] The rate of telomere sequence loss in human leukocytes varies with age [J].

Frenck, RW ;

Blackburn, EH ;

Shannon, KM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5607-5610

[7] ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma [J].

Gudbjartsson, Daniel F. ;

Sulem, Patrick ;

Stacey, Simon N. ;

Goldstein, Alisa M. ;

Rafnar, Thorunn ;

Sigurgeirsson, Bardur ;

Benediktsdottir, Kristrun R. ;

Thorisdottir, Kristin ;

Ragnarsson, Rafn ;

Sveinsdottir, Steinunn G. ;

Magnusson, Veronica ;

Lindblom, Annika ;

Kostulas, Konstantinos ;

Botella-Estrada, Rafael ;

Soriano, Virtudes ;

Juberias, Pablo ;

Grasa, Matilde ;

Saez, Berta ;

Andres, Raquel ;

Scherer, Dominique ;

Rudnai, Peter ;

Gurzau, Eugene ;

Koppova, Kvetoslava ;

Kiemeney, Lambertus A. ;

Jakobsdottir, Margret ;

Steinberg, Stacy ;

Helgason, Agnar ;

Gretarsdottir, Solveig ;

Tucker, Margaret A. ;

Mayordomo, Jose I. ;

Nagore, Eduardo ;

Kumar, Rajiv ;

Hansson, Johan ;

Olafsson, Jon H. ;

Gulcher, Jeffrey ;

Kong, Augustine ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE GENETICS, 2008, 40 (07) :886-891

[8] Many sequence variants affecting diversity of adult human height [J].

Gudbjartsson, Daniel F. ;

Walters, G. Bragi ;

Thorleifsson, Gudmar ;

Stefansson, Hreinn ;

Halldorsson, Bjarni V. ;

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