A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

Nathaniel Rothman; Montserrat Garcia-Closas; Nilanjan Chatterjee; Nuria Malats; Xifeng Wu; Jonine D. Figueroa; Francisco X. Real; David Van Den Berg; Giuseppe Matullo; Dalsu Baris; Michael Thun; Lambertus A. Kiemeney; Paolo Vineis; Immaculata De Vivo; Demetrius Albanes; Mark P. Purdue; Thorunn Rafnar; Michelle A.T. Hildebrandt; Anne E. Kiltie; Olivier Cussenot; Klaus Golka; Rajiv Kumar; Jack A. Taylor; Jose I. Mayordomo; Kevin B. Jacobs; Manolis Kogevinas; Amy Hutchinson; Zhaoming Wang; Yi Ping Fu; Ludmila Prokunina-Oolsson; Laurie BurdeT; Meredith Yeager; William Wheeler; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-Cclosas; Josep Loreta; Alison Johnson; Molly Schwenn; Margaret R. Karagas; Alan Schned; Gerald Andriole; Robert Grubb; Amanda Black; Eric J. Jacobs; W. Ryan Diver; Susan M. Gapstur; Stephanie J. Weinstein; Jarmo Virtamo; Victoria K. Cortessis; Manuela Gago-Dominguez; Malcolm C. Pike; Mariana C. Stern; Jian Min Yuan; David J. Hunter; Monica McGgrath; Colin P. Dinney; Bogdan Czerniak; Meng Chen; Hushan Yang; Sita H. Vermeulen; Katja K. Aben; J. Alfred Witjes; Remco R. MaKinje; Patrick Sulem; Soren Besenbacher; Kari Stefansson; Elio Riboli; Paul Brennan; Salvatore Panico; Carmen Navarro; Naomi E. Allen; H. Bas Bueno-De-Mesquita; Dimitrios Trichopoulos; Neil Caporaso; Maria Teresa Landi; Federico Canzian; Borje Ljungberg; Anne Tjonneland; Francoise Clavel-Chapelon; David T. Bishop; Mark T.W. Teo; Margaret A. Knowles; Simonetta Guarrera; Silvia Polidoro; Fulvio Ricceri; Carlotta Sacerdote; Alessandra Allione; Geraldine Cancel-Tassin; Silvia Selinski; Jan G. Hengstler; Holger Dietrich; Tony Fletcher; Peter Rudnai; Eugen Gurzau; Kvetoslava Koppova; Sophia C.E. Bolick; Ashley Godfrey; Zongli Xu; José I. Sanz-Velez; María D.García Prats; Manuel Sanchez; Gabriel Valdivia; Stefano Porru; Simone Benhamou; Robert N. Hoover; Joseph F. Fraumeni; Debra T. Silverman; Stephen J. Chanock

doi:10.1038/ng.687

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

Nathaniel Rothman, Montserrat Garcia-Closas, Nilanjan Chatterjee, Nuria Malats, Xifeng Wu, Jonine D. Figueroa, Francisco X. Real, David Van Den Berg, Giuseppe Matullo, Dalsu Baris, Michael Thun, Lambertus A. Kiemeney, Paolo Vineis, Immaculata De Vivo, Demetrius Albanes, Mark P. Purdue, Thorunn Rafnar, Michelle A.T. Hildebrandt, Anne E. Kiltie, Olivier CussenotKlaus Golka, Rajiv Kumar, Jack A. Taylor, Jose I. Mayordomo, Kevin B. Jacobs, Manolis Kogevinas, Amy Hutchinson, Zhaoming Wang, Yi Ping Fu, Ludmila Prokunina-Oolsson, Laurie BurdeT, Meredith Yeager, William Wheeler, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Cclosas, Josep Loreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Eric J. Jacobs, W. Ryan Diver, Susan M. Gapstur, Stephanie J. Weinstein, Jarmo Virtamo, Victoria K. Cortessis, Manuela Gago-Dominguez, Malcolm C. Pike, Mariana C. Stern, Jian Min Yuan, David J. Hunter, Monica McGgrath, Colin P. Dinney, Bogdan Czerniak, Meng Chen, Hushan Yang, Sita H. Vermeulen, Katja K. Aben, J. Alfred Witjes, Remco R. MaKinje, Patrick Sulem, Soren Besenbacher, Kari Stefansson, Elio Riboli, Paul Brennan, Salvatore Panico, Carmen Navarro, Naomi E. Allen, H. Bas Bueno-De-Mesquita, Dimitrios Trichopoulos, Neil Caporaso, Maria Teresa Landi, Federico Canzian, Borje Ljungberg, Anne Tjonneland, Francoise Clavel-Chapelon, David T. Bishop, Mark T.W. Teo, Margaret A. Knowles, Simonetta Guarrera, Silvia Polidoro, Fulvio Ricceri, Carlotta Sacerdote, Alessandra Allione, Geraldine Cancel-Tassin, Silvia Selinski, Jan G. Hengstler, Holger Dietrich, Tony Fletcher, Peter Rudnai, Eugen Gurzau, Kvetoslava Koppova, Sophia C.E. Bolick, Ashley Godfrey, Zongli Xu, José I. Sanz-Velez, María D.García Prats, Manuel Sanchez, Gabriel Valdivia, Stefano Porru, Simone Benhamou, Robert N. Hoover, Joseph F. Fraumeni, Debra T. Silverman, Stephen J. Chanock

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Abstract

We conducted a multi-stage, genome-wide aSociation study of blaDer cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies foLowed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified thrE new regions aSociated with blaDer cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8-10^-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2-10-11) on 19q12 maps to CNE1 and rs11892031 (P = 1-10-7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide aSociations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate aSociations for the GSTM1 deletion (P = 4-10-11) and a tag SNP for NAT2 acetylation status (P = 4-10-11), and found interactions with smoking in both regions. Our findings on coMon variants aSociated with blaDer cancer risk should provide new insights into the mechanisms of carcinogenesis.

Original language	English (US)
Pages (from-to)	978-984
Number of pages	7
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.687
State	Published - Nov 1 2010

ASJC Scopus subject areas

Genetics

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Rothman, N., Garcia-Closas, M., Chatterjee, N., Malats, N., Wu, X., Figueroa, J. D., Real, F. X., Van Den Berg, D., Matullo, G., Baris, D., Thun, M., Kiemeney, L. A., Vineis, P., De Vivo, I., Albanes, D., Purdue, M. P., Rafnar, T., Hildebrandt, M. A. T., Kiltie, A. E., ... Chanock, S. J. (2010). A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nature Genetics, 42(11), 978-984. https://doi.org/10.1038/ng.687

Rothman, N, Garcia-Closas, M, Chatterjee, N, Malats, N, Wu, X, Figueroa, JD, Real, FX, Van Den Berg, D, Matullo, G, Baris, D, Thun, M, Kiemeney, LA, Vineis, P, De Vivo, I, Albanes, D, Purdue, MP, Rafnar, T, Hildebrandt, MAT, Kiltie, AE, Cussenot, O, Golka, K, Kumar, R, Taylor, JA, Mayordomo, JI, Jacobs, KB, Kogevinas, M, Hutchinson, A, Wang, Z, Fu, YP, Prokunina-Oolsson, L, BurdeT, L, Yeager, M, Wheeler, W, Tardón, A, Serra, C, Carrato, A, García-Cclosas, R, Loreta, J, Johnson, A, Schwenn, M, Karagas, MR, Schned, A, Andriole, G, Grubb, R, Black, A, Jacobs, EJ, Diver, WR, Gapstur, SM, Weinstein, SJ, Virtamo, J, Cortessis, VK, Gago-Dominguez, M, Pike, MC, Stern, MC, Yuan, JM, Hunter, DJ, McGgrath, M, Dinney, CP , Czerniak, B, Chen, M, Yang, H, Vermeulen, SH, Aben, KK, Witjes, JA, MaKinje, RR, Sulem, P, Besenbacher, S, Stefansson, K, Riboli, E, Brennan, P, Panico, S, Navarro, C, Allen, NE, Bueno-De-Mesquita, HB, Trichopoulos, D, Caporaso, N, Landi, MT, Canzian, F, Ljungberg, B, Tjonneland, A, Clavel-Chapelon, F, Bishop, DT, Teo, MTW, Knowles, MA, Guarrera, S, Polidoro, S, Ricceri, F, Sacerdote, C, Allione, A, Cancel-Tassin, G, Selinski, S, Hengstler, JG, Dietrich, H, Fletcher, T, Rudnai, P, Gurzau, E, Koppova, K, Bolick, SCE, Godfrey, A, Xu, Z, Sanz-Velez, JI, Prats, MDG, Sanchez, M, Valdivia, G, Porru, S, Benhamou, S, Hoover, RN, Fraumeni, JF, Silverman, DT & Chanock, SJ 2010, 'A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci', Nature Genetics, vol. 42, no. 11, pp. 978-984. https://doi.org/10.1038/ng.687

@article{227f9245691a427790ba090d90890b0d,

title = "A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci",

abstract = "We conducted a multi-stage, genome-wide aSociation study of blaDer cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies foLowed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified thrE new regions aSociated with blaDer cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8-10-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2-10-11) on 19q12 maps to CNE1 and rs11892031 (P = 1-10-7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide aSociations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate aSociations for the GSTM1 deletion (P = 4-10-11) and a tag SNP for NAT2 acetylation status (P = 4-10-11), and found interactions with smoking in both regions. Our findings on coMon variants aSociated with blaDer cancer risk should provide new insights into the mechanisms of carcinogenesis.",

author = "Nathaniel Rothman and Montserrat Garcia-Closas and Nilanjan Chatterjee and Nuria Malats and Xifeng Wu and Figueroa, {Jonine D.} and Real, {Francisco X.} and {Van Den Berg}, David and Giuseppe Matullo and Dalsu Baris and Michael Thun and Kiemeney, {Lambertus A.} and Paolo Vineis and {De Vivo}, Immaculata and Demetrius Albanes and Purdue, {Mark P.} and Thorunn Rafnar and Hildebrandt, {Michelle A.T.} and Kiltie, {Anne E.} and Olivier Cussenot and Klaus Golka and Rajiv Kumar and Taylor, {Jack A.} and Mayordomo, {Jose I.} and Jacobs, {Kevin B.} and Manolis Kogevinas and Amy Hutchinson and Zhaoming Wang and Fu, {Yi Ping} and Ludmila Prokunina-Oolsson and Laurie BurdeT and Meredith Yeager and William Wheeler and Adonina Tard{\'o}n and Consol Serra and Alfredo Carrato and Reina Garc{\'i}a-Cclosas and Josep Loreta and Alison Johnson and Molly Schwenn and Karagas, {Margaret R.} and Alan Schned and Gerald Andriole and Robert Grubb and Amanda Black and Jacobs, {Eric J.} and Diver, {W. Ryan} and Gapstur, {Susan M.} and Weinstein, {Stephanie J.} and Jarmo Virtamo and Cortessis, {Victoria K.} and Manuela Gago-Dominguez and Pike, {Malcolm C.} and Stern, {Mariana C.} and Yuan, {Jian Min} and Hunter, {David J.} and Monica McGgrath and Dinney, {Colin P.} and Bogdan Czerniak and Meng Chen and Hushan Yang and Vermeulen, {Sita H.} and Aben, {Katja K.} and Witjes, {J. Alfred} and MaKinje, {Remco R.} and Patrick Sulem and Soren Besenbacher and Kari Stefansson and Elio Riboli and Paul Brennan and Salvatore Panico and Carmen Navarro and Allen, {Naomi E.} and Bueno-De-Mesquita, {H. Bas} and Dimitrios Trichopoulos and Neil Caporaso and Landi, {Maria Teresa} and Federico Canzian and Borje Ljungberg and Anne Tjonneland and Francoise Clavel-Chapelon and Bishop, {David T.} and Teo, {Mark T.W.} and Knowles, {Margaret A.} and Simonetta Guarrera and Silvia Polidoro and Fulvio Ricceri and Carlotta Sacerdote and Alessandra Allione and Geraldine Cancel-Tassin and Silvia Selinski and Hengstler, {Jan G.} and Holger Dietrich and Tony Fletcher and Peter Rudnai and Eugen Gurzau and Kvetoslava Koppova and Bolick, {Sophia C.E.} and Ashley Godfrey and Zongli Xu and Sanz-Velez, {Jos{\'e} I.} and Prats, {Mar{\'i}a D.Garc{\'i}a} and Manuel Sanchez and Gabriel Valdivia and Stefano Porru and Simone Benhamou and Hoover, {Robert N.} and Fraumeni, {Joseph F.} and Silverman, {Debra T.} and Chanock, {Stephen J.}",

note = "Funding Information: The bladder cancer GWAS was supported by the intramural research program of the US National Institutes of Health, National Cancer Institute. Funding Information: This project has been funded in part with federal funds from the National Cancer Institute, US National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. Please see Supplementary Note for information on support for individual studies that participated in the effort.",

year = "2010",

month = nov,

day = "1",

doi = "10.1038/ng.687",

language = "English (US)",

volume = "42",

pages = "978--984",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

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TY - JOUR

T1 - A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

AU - Rothman, Nathaniel

AU - Garcia-Closas, Montserrat

AU - Chatterjee, Nilanjan

AU - Malats, Nuria

AU - Wu, Xifeng

AU - Figueroa, Jonine D.

AU - Real, Francisco X.

AU - Van Den Berg, David

AU - Matullo, Giuseppe

AU - Baris, Dalsu

AU - Thun, Michael

AU - Kiemeney, Lambertus A.

AU - Vineis, Paolo

AU - De Vivo, Immaculata

AU - Albanes, Demetrius

AU - Purdue, Mark P.

AU - Rafnar, Thorunn

AU - Hildebrandt, Michelle A.T.

AU - Kiltie, Anne E.

AU - Cussenot, Olivier

AU - Golka, Klaus

AU - Kumar, Rajiv

AU - Taylor, Jack A.

AU - Mayordomo, Jose I.

AU - Jacobs, Kevin B.

AU - Kogevinas, Manolis

AU - Hutchinson, Amy

AU - Wang, Zhaoming

AU - Fu, Yi Ping

AU - Prokunina-Oolsson, Ludmila

AU - BurdeT, Laurie

AU - Yeager, Meredith

AU - Wheeler, William

AU - Tardón, Adonina

AU - Serra, Consol

AU - Carrato, Alfredo

AU - García-Cclosas, Reina

AU - Loreta, Josep

AU - Johnson, Alison

AU - Schwenn, Molly

AU - Karagas, Margaret R.

AU - Schned, Alan

AU - Andriole, Gerald

AU - Grubb, Robert

AU - Black, Amanda

AU - Jacobs, Eric J.

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Cortessis, Victoria K.

AU - Gago-Dominguez, Manuela

AU - Pike, Malcolm C.

AU - Stern, Mariana C.

AU - Yuan, Jian Min

AU - Hunter, David J.

AU - McGgrath, Monica

AU - Dinney, Colin P.

AU - Czerniak, Bogdan

AU - Chen, Meng

AU - Yang, Hushan

AU - Vermeulen, Sita H.

AU - Aben, Katja K.

AU - Witjes, J. Alfred

AU - MaKinje, Remco R.

AU - Sulem, Patrick

AU - Besenbacher, Soren

AU - Stefansson, Kari

AU - Riboli, Elio

AU - Brennan, Paul

AU - Panico, Salvatore

AU - Navarro, Carmen

AU - Allen, Naomi E.

AU - Bueno-De-Mesquita, H. Bas

AU - Trichopoulos, Dimitrios

AU - Caporaso, Neil

AU - Landi, Maria Teresa

AU - Canzian, Federico

AU - Ljungberg, Borje

AU - Tjonneland, Anne

AU - Clavel-Chapelon, Francoise

AU - Bishop, David T.

AU - Teo, Mark T.W.

AU - Knowles, Margaret A.

AU - Guarrera, Simonetta

AU - Polidoro, Silvia

AU - Ricceri, Fulvio

AU - Sacerdote, Carlotta

AU - Allione, Alessandra

AU - Cancel-Tassin, Geraldine

AU - Selinski, Silvia

AU - Hengstler, Jan G.

AU - Dietrich, Holger

AU - Fletcher, Tony

AU - Rudnai, Peter

AU - Gurzau, Eugen

AU - Koppova, Kvetoslava

AU - Bolick, Sophia C.E.

AU - Godfrey, Ashley

AU - Xu, Zongli

AU - Sanz-Velez, José I.

AU - Prats, María D.García

AU - Sanchez, Manuel

AU - Valdivia, Gabriel

AU - Porru, Stefano

AU - Benhamou, Simone

AU - Hoover, Robert N.

AU - Fraumeni, Joseph F.

AU - Silverman, Debra T.

AU - Chanock, Stephen J.

N1 - Funding Information: The bladder cancer GWAS was supported by the intramural research program of the US National Institutes of Health, National Cancer Institute. Funding Information: This project has been funded in part with federal funds from the National Cancer Institute, US National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. Please see Supplementary Note for information on support for individual studies that participated in the effort.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - We conducted a multi-stage, genome-wide aSociation study of blaDer cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies foLowed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified thrE new regions aSociated with blaDer cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8-10-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2-10-11) on 19q12 maps to CNE1 and rs11892031 (P = 1-10-7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide aSociations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate aSociations for the GSTM1 deletion (P = 4-10-11) and a tag SNP for NAT2 acetylation status (P = 4-10-11), and found interactions with smoking in both regions. Our findings on coMon variants aSociated with blaDer cancer risk should provide new insights into the mechanisms of carcinogenesis.

AB - We conducted a multi-stage, genome-wide aSociation study of blaDer cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies foLowed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified thrE new regions aSociated with blaDer cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8-10-12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2-10-11) on 19q12 maps to CNE1 and rs11892031 (P = 1-10-7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide aSociations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate aSociations for the GSTM1 deletion (P = 4-10-11) and a tag SNP for NAT2 acetylation status (P = 4-10-11), and found interactions with smoking in both regions. Our findings on coMon variants aSociated with blaDer cancer risk should provide new insights into the mechanisms of carcinogenesis.

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U2 - 10.1038/ng.687

DO - 10.1038/ng.687

M3 - Article

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AN - SCOPUS:84947899485

SN - 1061-4036

VL - 42

SP - 978

EP - 984

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

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