Genome-wide association study identifies multiple loci associated with bladder cancer risk

Jonine D. Figueroa; Yuanqing Ye; Afshan Siddiq; Montserrat Garcia-closas; Nilanjan Chatterjee; Ludmila Prokunina-olsson; Victoria K. Cortessis; Charles Kooperberg; Olivier Cussenot; Simone Benhamou; Jennifer Prescott; Stefano Porru; Colin P. Dinney; Núria Malats; Dalsu Baris; Mark Purdue; Eric J. Jacobs; Demetrius Albanes; Zhaoming Wang; Xiang Deng; Charles C. Chung; Wei Tang; H. Bas bueno-de-mesquita; Dimitrios Trichopoulos; Börje Ljungberg; Françoise Clavel-chapelon; Elisabete Weiderpass; Vittorio Krogh; Miren Dorronsoro; Ruth Travis; Anne Tjønneland; Paul Brenan; Jenny Chang-claude; Elio Riboli; David Conti; Manuela Gago-dominguez; Mariana C. Stern; Malcolm C. Pike; David Van den berg; Jian Min Yuan; Chancellor Hohensee; Rebecca Rodabough; Geraldine Cancel-tassin; Morgan Roupret; Eva Comperat; Constance Chen; Immaculata De vivo; Edward Giovannucci; David J. Hunter; Peter Kraft; Sara Lindstrom; Angela Carta; Sofia Pavanello; Cecilia Arici; Giuseppe Mastrangelo; Ashish M. Kamat; Seth P. Lerner; H. Barton grossman; Jie Lin; Jian Gu; Xia Pu; Amy Hutchinson; Laurie Burdette; William Wheeler; Manolis Kogevinas; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-closas; Josep Lloreta; Molly Schwenn; Margaret R. Karagas; Alison Johnson; Alan Schned; Karla R. Armenti; G. M. Hosain; Gerald Andriole; Robert Grubb; Amanda Black; W. Ryan Diver; Susan M. Gapstur; Stephanie J. Weinstein; Jarmo Virtamo; Chris A. Haiman; Maria T. Landi; Neil Caporaso; Joseph F. Fraumeni; Paolo Vineis; Xifeng Wu; Debra T. Silverman; Stephen Chanock; Nathaniel Rothman

doi:10.1093/hmg/ddt519

Genome-wide association study identifies multiple loci associated with bladder cancer risk

Jonine D. Figueroa, Yuanqing Ye, Afshan Siddiq, Montserrat Garcia-closas, Nilanjan Chatterjee, Ludmila Prokunina-olsson, Victoria K. Cortessis, Charles Kooperberg, Olivier Cussenot, Simone Benhamou, Jennifer Prescott, Stefano Porru, Colin P. Dinney, Núria Malats, Dalsu Baris, Mark Purdue, Eric J. Jacobs, Demetrius Albanes, Zhaoming Wang, Xiang DengCharles C. Chung, Wei Tang, H. Bas bueno-de-mesquita, Dimitrios Trichopoulos, Börje Ljungberg, Françoise Clavel-chapelon, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth Travis, Anne Tjønneland, Paul Brenan, Jenny Chang-claude, Elio Riboli, David Conti, Manuela Gago-dominguez, Mariana C. Stern, Malcolm C. Pike, David Van den berg, Jian Min Yuan, Chancellor Hohensee, Rebecca Rodabough, Geraldine Cancel-tassin, Morgan Roupret, Eva Comperat, Constance Chen, Immaculata De vivo, Edward Giovannucci, David J. Hunter, Peter Kraft, Sara Lindstrom, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, Ashish M. Kamat, Seth P. Lerner, H. Barton grossman, Jie Lin, Jian Gu, Xia Pu, Amy Hutchinson, Laurie Burdette, William Wheeler, Manolis Kogevinas, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-closas, Josep Lloreta, Molly Schwenn, Margaret R. Karagas, Alison Johnson, Alan Schned, Karla R. Armenti, G. M. Hosain, Gerald Andriole, Robert Grubb, Amanda Black, W. Ryan Diver, Susan M. Gapstur, Stephanie J. Weinstein, Jarmo Virtamo, Chris A. Haiman, Maria T. Landi, Neil Caporaso, Joseph F. Fraumeni, Paolo Vineis, Xifeng Wu, Debra T. Silverman, Stephen Chanock, Nathaniel Rothman

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10^-5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10^-9) and rs907611 on 11p15.5 (P = 4.11 × 10^-8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10^-7) and rs4510656 on 6p22.3 (P = 6.98 × 10^-7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Original language	English (US)
Article number	ddt519
Journal	Human molecular genetics
Volume	23
Issue number	5
DOIs	https://doi.org/10.1093/hmg/ddt519
State	Published - Mar 2014
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1093/hmg/ddt519

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Figueroa, J. D., Ye, Y., Siddiq, A., Garcia-closas, M., Chatterjee, N., Prokunina-olsson, L., Cortessis, V. K., Kooperberg, C., Cussenot, O., Benhamou, S., Prescott, J., Porru, S., Dinney, C. P., Malats, N., Baris, D., Purdue, M., Jacobs, E. J., Albanes, D., Wang, Z., ... Rothman, N. (2014). Genome-wide association study identifies multiple loci associated with bladder cancer risk. Human molecular genetics, 23(5), Article ddt519. https://doi.org/10.1093/hmg/ddt519

Figueroa, JD, Ye, Y, Siddiq, A, Garcia-closas, M, Chatterjee, N, Prokunina-olsson, L, Cortessis, VK, Kooperberg, C, Cussenot, O, Benhamou, S, Prescott, J, Porru, S, Dinney, CP, Malats, N, Baris, D, Purdue, M, Jacobs, EJ, Albanes, D, Wang, Z, Deng, X, Chung, CC, Tang, W, Bas bueno-de-mesquita, H, Trichopoulos, D, Ljungberg, B, Clavel-chapelon, F, Weiderpass, E, Krogh, V, Dorronsoro, M, Travis, R, Tjønneland, A, Brenan, P, Chang-claude, J, Riboli, E, Conti, D, Gago-dominguez, M, Stern, MC, Pike, MC, Van den berg, D, Yuan, JM, Hohensee, C, Rodabough, R, Cancel-tassin, G, Roupret, M, Comperat, E, Chen, C, De vivo, I, Giovannucci, E, Hunter, DJ, Kraft, P, Lindstrom, S, Carta, A, Pavanello, S, Arici, C, Mastrangelo, G, Kamat, AM, Lerner, SP, Barton grossman, H, Lin, J, Gu, J, Pu, X, Hutchinson, A, Burdette, L, Wheeler, W, Kogevinas, M, Tardón, A, Serra, C, Carrato, A, García-closas, R, Lloreta, J, Schwenn, M, Karagas, MR, Johnson, A, Schned, A, Armenti, KR, Hosain, GM, Andriole, G, Grubb, R, Black, A, Ryan Diver, W, Gapstur, SM, Weinstein, SJ, Virtamo, J, Haiman, CA, Landi, MT, Caporaso, N, Fraumeni, JF, Vineis, P, Wu, X, Silverman, DT, Chanock, S & Rothman, N 2014, 'Genome-wide association study identifies multiple loci associated with bladder cancer risk', Human molecular genetics, vol. 23, no. 5, ddt519. https://doi.org/10.1093/hmg/ddt519

@article{1011081e8d224d1c98a04141f9d00e64,

title = "Genome-wide association study identifies multiple loci associated with bladder cancer risk",

abstract = "Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10-5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10-9) and rs907611 on 11p15.5 (P = 4.11 × 10-8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10-7) and rs4510656 on 6p22.3 (P = 6.98 × 10-7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.",

author = "Figueroa, {Jonine D.} and Yuanqing Ye and Afshan Siddiq and Montserrat Garcia-closas and Nilanjan Chatterjee and Ludmila Prokunina-olsson and Cortessis, {Victoria K.} and Charles Kooperberg and Olivier Cussenot and Simone Benhamou and Jennifer Prescott and Stefano Porru and Dinney, {Colin P.} and N{\'u}ria Malats and Dalsu Baris and Mark Purdue and Jacobs, {Eric J.} and Demetrius Albanes and Zhaoming Wang and Xiang Deng and Chung, {Charles C.} and Wei Tang and {Bas bueno-de-mesquita}, H. and Dimitrios Trichopoulos and B{\"o}rje Ljungberg and Fran{\c c}oise Clavel-chapelon and Elisabete Weiderpass and Vittorio Krogh and Miren Dorronsoro and Ruth Travis and Anne Tj{\o}nneland and Paul Brenan and Jenny Chang-claude and Elio Riboli and David Conti and Manuela Gago-dominguez and Stern, {Mariana C.} and Pike, {Malcolm C.} and {Van den berg}, David and Yuan, {Jian Min} and Chancellor Hohensee and Rebecca Rodabough and Geraldine Cancel-tassin and Morgan Roupret and Eva Comperat and Constance Chen and {De vivo}, Immaculata and Edward Giovannucci and Hunter, {David J.} and Peter Kraft and Sara Lindstrom and Angela Carta and Sofia Pavanello and Cecilia Arici and Giuseppe Mastrangelo and Kamat, {Ashish M.} and Lerner, {Seth P.} and {Barton grossman}, H. and Jie Lin and Jian Gu and Xia Pu and Amy Hutchinson and Laurie Burdette and William Wheeler and Manolis Kogevinas and Adonina Tard{\'o}n and Consol Serra and Alfredo Carrato and Reina Garc{\'i}a-closas and Josep Lloreta and Molly Schwenn and Karagas, {Margaret R.} and Alison Johnson and Alan Schned and Armenti, {Karla R.} and Hosain, {G. M.} and Gerald Andriole and Robert Grubb and Amanda Black and {Ryan Diver}, W. and Gapstur, {Susan M.} and Weinstein, {Stephanie J.} and Jarmo Virtamo and Haiman, {Chris A.} and Landi, {Maria T.} and Neil Caporaso and Fraumeni, {Joseph F.} and Paolo Vineis and Xifeng Wu and Silverman, {Debra T.} and Stephen Chanock and Nathaniel Rothman",

note = "Funding Information: Funding support for individual studies that participated in the effort is as follows: ATBC (D.A.)—This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. Additionally, this research was supported by US Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services. EPIC (P.V.)—ICL—Europe Against Cancer Program of the European Commission (SANCO); IARC— International Agency for Research on Cancer; France—Ligue contre le Cancer Societe 3M, Mutuelle Generale de l{\textquoteright}Education Nationale; Institut National de la Sant{\'e} et de la Recherche M{\'e}d-icale (INSERM); Italy—Italian Association for Research on Cancer National Research Council; Spain—Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiolog{\'i}a y Salud P{\'u}blica (CIBERESP), Spain; ISCIII RETIC (RD06/0020); Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (N 6236) and Navarra and the Catalan Institute of Oncology; UK—Cancer Research UK Medical Research Council with additional support from the Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust; The Netherlands—Dutch Ministry of Public Health Dutch Prevention Funds LK Research Funds Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); Greece— Hellenic Ministry of Health, the Stavros Niarchos Foundation and the Hellenic Health Foundation; Germany—German Cancer Aid, German Cancer Research Center Federal Ministry of Education and Research (Grant 01-EA-9401); Sweden— Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden and Denmark—Danish Cancer Society. FBCS (S.B.)—Ligue Contre le Cancer du Val-de-Marne; Fondation de France; Groupement d{\textquoteright}Entreprises Franc¸aises dans la Lutte contre le Cancer; Association pour la Recherche sur le Cancer, France (TXBCS—U01 CA 127615 (X.W.), R01 CA 74880 (X.W.) and P50 CA 91846 (X.W. and C.P.D.), UT MD Anderson Cancer Centre Research Trust (X.W.), Centre for Translational and Public Health Genomics at MD Anderson Cancer Centre. LABCS (M.P.)—NIH (grants R01CA65726, R01CA114665, 1R01CA114665 and 1P01CA86871). NEBCS (D.T.S.)—Intramural research program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-01037. NHS and HPFS (I.D.V.)—CA055075, P01 CA87969, R01 CA49449, UM1 CA176726, R01 CA67262 and UM1 CA167552. PLCO (M.P.P.)—The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C), and study coordination at the GENEVA (N.C.) Coordination Center (U01HG004446) for the genotyping of the lung studies with controls from EAGLE study and part of the PLCO. Genotyping for the remaining part of PLCO and all ATBC and CPS-II samples were supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. SBCS (D.T.S.)—Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-11015. FIS/Spain 98/1274, FIS/Spain 00/0745, PI061614 and G03/174, Fundaci{\'o} Marat{\'o} TV3, Red Tem{\'a}tica Investigaci{\'o}n Cooperativa en C{\'a}ncer (RTICC), Consol{\'i}der ONCOBIO, EU-FP7-201663; and RO1-CA089715 and CA34627. WHI (C.K.)—The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN26820 1100001C, HHSN268201100002C, HHSN268201100003C, HH SN268201100004C and HHSN271201100004C.",

year = "2014",

month = mar,

doi = "10.1093/hmg/ddt519",

language = "English (US)",

volume = "23",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Genome-wide association study identifies multiple loci associated with bladder cancer risk

AU - Figueroa, Jonine D.

AU - Ye, Yuanqing

AU - Siddiq, Afshan

AU - Garcia-closas, Montserrat

AU - Chatterjee, Nilanjan

AU - Prokunina-olsson, Ludmila

AU - Cortessis, Victoria K.

AU - Kooperberg, Charles

AU - Cussenot, Olivier

AU - Benhamou, Simone

AU - Prescott, Jennifer

AU - Porru, Stefano

AU - Dinney, Colin P.

AU - Malats, Núria

AU - Baris, Dalsu

AU - Purdue, Mark

AU - Jacobs, Eric J.

AU - Albanes, Demetrius

AU - Wang, Zhaoming

AU - Deng, Xiang

AU - Chung, Charles C.

AU - Tang, Wei

AU - Bas bueno-de-mesquita, H.

AU - Trichopoulos, Dimitrios

AU - Ljungberg, Börje

AU - Clavel-chapelon, Françoise

AU - Weiderpass, Elisabete

AU - Krogh, Vittorio

AU - Dorronsoro, Miren

AU - Travis, Ruth

AU - Tjønneland, Anne

AU - Brenan, Paul

AU - Chang-claude, Jenny

AU - Riboli, Elio

AU - Conti, David

AU - Gago-dominguez, Manuela

AU - Stern, Mariana C.

AU - Pike, Malcolm C.

AU - Van den berg, David

AU - Yuan, Jian Min

AU - Hohensee, Chancellor

AU - Rodabough, Rebecca

AU - Cancel-tassin, Geraldine

AU - Roupret, Morgan

AU - Comperat, Eva

AU - Chen, Constance

AU - De vivo, Immaculata

AU - Giovannucci, Edward

AU - Hunter, David J.

AU - Kraft, Peter

AU - Lindstrom, Sara

AU - Carta, Angela

AU - Pavanello, Sofia

AU - Arici, Cecilia

AU - Mastrangelo, Giuseppe

AU - Kamat, Ashish M.

AU - Lerner, Seth P.

AU - Barton grossman, H.

AU - Lin, Jie

AU - Gu, Jian

AU - Pu, Xia

AU - Hutchinson, Amy

AU - Burdette, Laurie

AU - Wheeler, William

AU - Kogevinas, Manolis

AU - Tardón, Adonina

AU - Serra, Consol

AU - Carrato, Alfredo

AU - García-closas, Reina

AU - Lloreta, Josep

AU - Schwenn, Molly

AU - Karagas, Margaret R.

AU - Johnson, Alison

AU - Schned, Alan

AU - Armenti, Karla R.

AU - Hosain, G. M.

AU - Andriole, Gerald

AU - Grubb, Robert

AU - Black, Amanda

AU - Ryan Diver, W.

AU - Gapstur, Susan M.

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Haiman, Chris A.

AU - Landi, Maria T.

AU - Caporaso, Neil

AU - Fraumeni, Joseph F.

AU - Vineis, Paolo

AU - Wu, Xifeng

AU - Silverman, Debra T.

AU - Chanock, Stephen

AU - Rothman, Nathaniel

N1 - Funding Information: Funding support for individual studies that participated in the effort is as follows: ATBC (D.A.)—This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. Additionally, this research was supported by US Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services. EPIC (P.V.)—ICL—Europe Against Cancer Program of the European Commission (SANCO); IARC— International Agency for Research on Cancer; France—Ligue contre le Cancer Societe 3M, Mutuelle Generale de l’Education Nationale; Institut National de la Santé et de la Recherche Méd-icale (INSERM); Italy—Italian Association for Research on Cancer National Research Council; Spain—Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; ISCIII RETIC (RD06/0020); Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (N 6236) and Navarra and the Catalan Institute of Oncology; UK—Cancer Research UK Medical Research Council with additional support from the Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust; The Netherlands—Dutch Ministry of Public Health Dutch Prevention Funds LK Research Funds Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); Greece— Hellenic Ministry of Health, the Stavros Niarchos Foundation and the Hellenic Health Foundation; Germany—German Cancer Aid, German Cancer Research Center Federal Ministry of Education and Research (Grant 01-EA-9401); Sweden— Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden and Denmark—Danish Cancer Society. FBCS (S.B.)—Ligue Contre le Cancer du Val-de-Marne; Fondation de France; Groupement d’Entreprises Franc¸aises dans la Lutte contre le Cancer; Association pour la Recherche sur le Cancer, France (TXBCS—U01 CA 127615 (X.W.), R01 CA 74880 (X.W.) and P50 CA 91846 (X.W. and C.P.D.), UT MD Anderson Cancer Centre Research Trust (X.W.), Centre for Translational and Public Health Genomics at MD Anderson Cancer Centre. LABCS (M.P.)—NIH (grants R01CA65726, R01CA114665, 1R01CA114665 and 1P01CA86871). NEBCS (D.T.S.)—Intramural research program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-01037. NHS and HPFS (I.D.V.)—CA055075, P01 CA87969, R01 CA49449, UM1 CA176726, R01 CA67262 and UM1 CA167552. PLCO (M.P.P.)—The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C), and study coordination at the GENEVA (N.C.) Coordination Center (U01HG004446) for the genotyping of the lung studies with controls from EAGLE study and part of the PLCO. Genotyping for the remaining part of PLCO and all ATBC and CPS-II samples were supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. SBCS (D.T.S.)—Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and intramural contract number NCI N02-CP-11015. FIS/Spain 98/1274, FIS/Spain 00/0745, PI061614 and G03/174, Fundació Marató TV3, Red Temática Investigación Cooperativa en Cáncer (RTICC), Consolíder ONCOBIO, EU-FP7-201663; and RO1-CA089715 and CA34627. WHI (C.K.)—The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN26820 1100001C, HHSN268201100002C, HHSN268201100003C, HH SN268201100004C and HHSN271201100004C.

PY - 2014/3

Y1 - 2014/3

N2 - Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10-5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10-9) and rs907611 on 11p15.5 (P = 4.11 × 10-8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10-7) and rs4510656 on 6p22.3 (P = 6.98 × 10-7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

AB - Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10-5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10-9) and rs907611 on 11p15.5 (P = 4.11 × 10-8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10-7) and rs4510656 on 6p22.3 (P = 6.98 × 10-7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84894054918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894054918&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddt519

DO - 10.1093/hmg/ddt519

M3 - Article

C2 - 24163127

AN - SCOPUS:84894054918

SN - 0964-6906

VL - 23

JO - Human molecular genetics

JF - Human molecular genetics

IS - 5

M1 - ddt519

ER -

Genome-wide association study identifies multiple loci associated with bladder cancer risk

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