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

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

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

University of Oxford

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

350 Citations (Scopus)

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
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
Publication status	Published - 1 Nov 2010

Bibliographical note

Funding Information:
The bladder cancer GWAS was supported by the intramural research program of the US National Institutes of Health, National Cancer Institute.

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.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.687

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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., ... Virtamo, 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 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{bd8716aecb9e496fb9037f86a3309625,

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",

note = "Funding Information: The bladder cancer GWAS was supported by the intramural research program of the US National Institutes of Health, National Cancer Institute. 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.",

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month = nov,

day = "1",

doi = "10.1038/ng.687",

language = "English",

volume = "42",

pages = "978--984",

journal = "Nature Genetics",

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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

N1 - Funding Information: The bladder cancer GWAS was supported by the intramural research program of the US National Institutes of Health, National Cancer Institute. 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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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

Abstract

Bibliographical note

UN SDGs

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