Letter | Published:

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

Nature Genetics volume 42, pages 978984 (2010) | Download Citation

Abstract

We conducted a multi-stage, genome-wide association study of bladder 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 followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder 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 CCNE1 and rs11892031 (P = 1 × 10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations 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 common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , , & Bladder cancer. in Cancer Epidemiology and Prevention (eds. Schottenfeld, D. and Fraumeni, J.F. Jr.) 1101–1127 (Oxford University Press, New York, 2006).

  2. 2.

    , , & Familial and environmental interactions in bladder cancer risk. Int. J. Cancer 35, 703–706 (1985).

  3. 3.

    et al. Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk? Cancer Epidemiol. Biomarkers Prev. 16, 1595–1600 (2007).

  4. 4.

    et al. Segregation analysis of urothelial cell carcinoma. Eur. J. Cancer 42, 1428–1433 (2006).

  5. 5.

    et al. N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark. Environ. Health Perspect. 29, 71–79 (1979).

  6. 6.

    et al. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J. Natl. Cancer Inst. 85, 1159–1164 (1993).

  7. 7.

    et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 366, 649–659 (2005).

  8. 8.

    , & Commentary: Reflections on G.M. Lower and colleagues' 1979 study associating slow acetylator phenotype with urinary bladder cancer: meta-analysis, historical refinements of the hypothesis, and lessons learned. Int. J. Epidemiol. 36, 23–28 (2007).

  9. 9.

    et al. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat. Genet. 40, 1307–1312 (2008).

  10. 10.

    et al. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat. Genet. 42, 415–419 (2010).

  11. 11.

    et al. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat. Genet. 41, 991–995 (2009).

  12. 12.

    et al. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat. Genet. 41, 1116–1121 (2009).

  13. 13.

    et al. Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat. Genet. 41, 1055–1057 (2009).

  14. 14.

    et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat. Genet. 42, 132–136 (2010).

  15. 15.

    et al. A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat. Genet. 40, 623–630 (2008).

  16. 16.

    et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087–1093 (2007).

  17. 17.

    et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat. Genet. 39, 989–994 (2007).

  18. 18.

    et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet. 39, 645–649 (2007).

  19. 19.

    et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet. 41, 221–227 (2009).

  20. 20.

    et al. New common variants affecting susceptibility to basal cell carcinoma. Nat. Genet. 41, 909–914 (2009).

  21. 21.

    et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am. J. Hum. Genet. 85, 679–691 (2009).

  22. 22.

    et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat. Genet. 41, 899–904 (2009).

  23. 23.

    et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet. 42, 224–228 (2010).

  24. 24.

    et al. Assessing the impact of population stratification on genetic association studies. Nat. Genet. 36, 388–393 (2004).

  25. 25.

    Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

  26. 26.

    et al. A single nucleotide polymorphism identified in a genome-wide scan tags variation in the N-acetyltransferase 2 phenotype in populations of European background. Pharmacogenet. Genomics published online, doi:10.1097/FPC.0b013e32833e1b54 (25 August 2010).

  27. 27.

    The AID/APOBEC family of nucleic acid mutators. Genome Biol. 9, 229 (2008).

  28. 28.

    & To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer 1, 222–231 (2001).

  29. 29.

    et al. High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. Am. J. Pathol. 157, 787–794 (2000).

  30. 30.

    , , & Family 1 uridine-5′-diphosphate glucuronosyltransferases (UGT1A): from Gilbert's syndrome to genetic organization and variability. Arch. Toxicol. 82, 415–433 (2008).

  31. 31.

    et al. Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res. 60, 6921–6926 (2000).

  32. 32.

    , & Differential down-regulation of the UDP-glucuronosyltransferase 1A locus is an early event in human liver and biliary cancer. Cancer Res. 57, 2979–2985 (1997).

  33. 33.

    , , & Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in human gastric epithelium. Mol. Pharmacol. 54, 647–654 (1998).

  34. 34.

    et al. Can down-regulation of UDP-glucuronosyltransferases in the urinary bladder tissue impact the risk of chemical carcinogenesis? Int. J. Cancer 91, 141–143 (2001).

  35. 35.

    et al. Suppression of AhR signaling pathway is associated with the down-regulation of UDP-glucuronosyltransferases during BBN-induced urinary bladder carcinogenesis in mice. J. Biochem. 147, 353–360 (2010).

  36. 36.

    & Telomere maintenance and human bone marrow failure. Blood 111, 4446–4455 (2008).

  37. 37.

    et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1317–1326 (2007).

  38. 38.

    et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc. Natl. Acad. Sci. USA 104, 7552–7557 (2007).

  39. 39.

    et al. Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc. Natl. Acad. Sci. USA 106, 1187–1192 (2009).

  40. 40.

    et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 42, 570–575 (2010).

  41. 41.

    N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 25, 1649–1658 (2006).

  42. 42.

    , & A note on exact tests of Hardy-Weinberg equilibrium. Am. J. Hum. Genet. 76, 887–893 (2005).

  43. 43.

    , & Inference of population structure using multilocus genotype data. Genetics 155, 945–959 (2000).

  44. 44.

    et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).

  45. 45.

    et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

  46. 46.

    , & Population structure and eigenanalysis. PLoS Genet. 2, e190 (2006).

  47. 47.

    et al. Population substructure and control selection in genome-wide association studies. PLoS ONE 3, e2551 (2008).

  48. 48.

    et al. Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum. Mol. Genet. 17, R122–R128 (2008).

  49. 49.

    , & Enhanced pedigree error detection. Hum. Hered. 54, 99–110 (2002).

  50. 50.

    Testing for association on the X chromosome. Biostatistics 9, 593–600 (2008).

  51. 51.

    SequenceLDhot: detecting recombination hotspots. Bioinformatics 22, 3061–3066 (2006).

  52. 52.

    , , , & Application of coalescent methods to reveal fine-scale rate variation and recombination hotspots. Genetics 167, 2067–2081 (2004).

Download references

Acknowledgements

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.

Author information

Author notes

    • Nathaniel Rothman
    • , Montserrat Garcia-Closas
    • , Nilanjan Chatterjee
    • , Nuria Malats
    •  & Xifeng Wu

    These authors contributed equally to this work.

    • 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

    These authors are the designated representatives of the participating studies.

    • Debra T Silverman
    •  & Stephen J Chanock

    These authors jointly directed this work.

Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

    • Nathaniel Rothman
    • , Montserrat Garcia-Closas
    • , Nilanjan Chatterjee
    • , Jonine D Figueroa
    • , Dalsu Baris
    • , Demetrius Albanes
    • , Mark P Purdue
    • , Yi-Ping Fu
    • , Ludmila Prokunina-Olsson
    • , Amanda Black
    • , Stephanie J Weinstein
    • , Neil Caporaso
    • , Maria Teresa Landi
    • , Robert N Hoover
    • , Joseph F Fraumeni Jr
    • , Debra T Silverman
    •  & Stephen J Chanock
  2. Spanish National Cancer Research Centre, Madrid, Spain.

    • Nuria Malats
    •  & Francisco X Real
  3. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Xifeng Wu
    • , Michelle A T Hildebrandt
    • , Meng Chen
    •  & Hushan Yang
  4. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

    • Francisco X Real
  5. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • David Van Den Berg
    • , Victoria K Cortessis
    • , Manuela Gago-Dominguez
    • , Malcolm C Pike
    •  & Mariana C Stern
  6. Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy.

    • Giuseppe Matullo
    •  & Fulvio Ricceri
  7. Human Genetics Foundation (HuGeF), Torino, Italy.

    • Giuseppe Matullo
    • , Paolo Vineis
    • , Simonetta Guarrera
    • , Silvia Polidoro
    • , Fulvio Ricceri
    • , Carlotta Sacerdote
    •  & Alessandra Allione
  8. Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.

    • Michael Thun
    • , Eric J Jacobs
    • , W Ryan Diver
    •  & Susan M Gapstur
  9. Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
    • , Sita H Vermeulen
    •  & Katja K Aben
  10. Comprehensive Cancer Center East, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
    •  & Katja K Aben
  11. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
    •  & J Alfred Witjes
  12. Imperial College London, London, UK.

    • Paolo Vineis
    •  & Elio Riboli
  13. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Immaculata De Vivo
  14. deCODE Genetics, Reykjavik, Iceland.

    • Thorunn Rafnar
    • , Patrick Sulem
    • , Soren Besenbacher
    •  & Kari Stefansson
  15. Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK.

    • Anne E Kiltie
  16. Department of Urology, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France.

    • Olivier Cussenot
  17. Centre de Recherche sur les Pathologies Prostatiques, Paris, France.

    • Olivier Cussenot
    •  & Geraldine Cancel-Tassin
  18. Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.

    • Klaus Golka
    • , Silvia Selinski
    •  & Jan G Hengstler
  19. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.

    • Rajiv Kumar
  20. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.

    • Jack A Taylor
    • , Sophia C E Bolick
    • , Ashley Godfrey
    •  & Zongli Xu
  21. University of Zaragoza, Zaragoza, Spain.

    • Jose I Mayordomo
    • , Manuel Sanchez
    •  & Gabriel Valdivia
  22. Core Genotype Facility, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland, USA.

    • Kevin B Jacobs
    • , Amy Hutchinson
    • , Zhaoming Wang
    • , Laurie Burdett
    •  & Meredith Yeager
  23. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

    • Manolis Kogevinas
  24. Municipal Institute of Medical Research, Barcelona, Spain.

    • Manolis Kogevinas
  25. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

    • Manolis Kogevinas
    • , Adonina Tardón
    •  & Carmen Navarro
  26. National School of Public Health, Athens, Greece.

    • Manolis Kogevinas
  27. Information Management Services, Inc., Rockville, Maryland, USA.

    • William Wheeler
  28. Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.

    • Adonina Tardón
  29. Universitat Pompeu Fabra, Barcelona, Spain.

    • Consol Serra
  30. Ramón y Cajal University Hospital, Madrid, Spain.

    • Alfredo Carrato
  31. Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain.

    • Reina García-Closas
  32. Hospital del Mar-Institut Municipal d'Investigació Mèdica (IMIM), Universitat Pompeu Fabra, Barcelona, Spain.

    • Josep Lloreta
  33. Vermont Cancer Registry, Burlington, Vermont, USA.

    • Alison Johnson
  34. Maine Cancer Registry, Augusta, Maine, USA.

    • Molly Schwenn
  35. Dartmouth Medical School, Hanover, New Hampshire, USA.

    • Margaret R Karagas
    •  & Alan Schned
  36. Department of Urology, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Gerald Andriole Jr
    •  & Robert Grubb III
  37. National Institute for Health and Welfare, Helsinki, Finland.

    • Jarmo Virtamo
  38. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Malcolm C Pike
  39. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.

    • Jian-Min Yuan
  40. Department of Epidemiology, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • David J Hunter
    •  & Monica McGrath
  41. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Colin P Dinney
  42. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Bogdan Czerniak
  43. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Sita H Vermeulen
    •  & Remco R Makkinje
  44. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Kari Stefansson
  45. International Agency for Research on Cancer, Lyon, France.

    • Paul Brennan
  46. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.

    • Salvatore Panico
  47. Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain.

    • Carmen Navarro
  48. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

    • Naomi E Allen
  49. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

    • H Bas Bueno-de-Mesquita
  50. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Dimitrios Trichopoulos
  51. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.

    • Dimitrios Trichopoulos
  52. Genomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.

    • Federico Canzian
  53. Department of Surgical and Perioperative Sciences, University of Umea, Umea, Sweden.

    • Borje Ljungberg
  54. Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark.

    • Anne Tjonneland
  55. Centre for Research in Epidemiology and Population Health, Institute Gustave-Roussy, Paris South University, Villejuif, France.

    • Francoise Clavel-Chapelon
  56. Leeds Institute of Molecular Medicine, St. James's University Hospital, University of Leeds, Leeds, UK.

    • David T Bishop
    • , Mark T W Teo
    •  & Margaret A Knowles
  57. Unit of Cancer Epidemiology, University of Torino, Torino, Italy.

    • Carlotta Sacerdote
  58. Department of Urology, Paul Gerhardt Foundation, Wittenberg, Germany.

    • Holger Dietrich
  59. Institute of Hygiene and Tropical Medicine, London, UK.

    • Tony Fletcher
  60. National Institute of Environmental Health, Budapest, Hungary.

    • Peter Rudnai
  61. Babes Bolyai University, Environmental Health Center, Cluj-Napoca, Romania.

    • Eugen Gurzau
  62. State Health Institute, Banská Bystrica, Slovakia.

    • Kvetoslava Koppova
  63. San Jorge University Hospital, Huesca, Spain.

    • José I Sanz-Velez
    •  & María D García-Prats
  64. Department of Experimental and Applied Medicine, Section of Occupational Medicine and Industrial Hygiene, University of Brescia, Brescia, Italy.

    • Stefano Porru
  65. Institut national de la santé et de la recherche médicale, U946, Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France.

    • Simone Benhamou
  66. Centre National de la Recherche Scientifique, UMR8200, Institut Gustave-Roussy, Villejuif, France.

    • Simone Benhamou

Authors

  1. Search for Nathaniel Rothman in:

  2. Search for Montserrat Garcia-Closas in:

  3. Search for Nilanjan Chatterjee in:

  4. Search for Nuria Malats in:

  5. Search for Xifeng Wu in:

  6. Search for Jonine D Figueroa in:

  7. Search for Francisco X Real in:

  8. Search for David Van Den Berg in:

  9. Search for Giuseppe Matullo in:

  10. Search for Dalsu Baris in:

  11. Search for Michael Thun in:

  12. Search for Lambertus A Kiemeney in:

  13. Search for Paolo Vineis in:

  14. Search for Immaculata De Vivo in:

  15. Search for Demetrius Albanes in:

  16. Search for Mark P Purdue in:

  17. Search for Thorunn Rafnar in:

  18. Search for Michelle A T Hildebrandt in:

  19. Search for Anne E Kiltie in:

  20. Search for Olivier Cussenot in:

  21. Search for Klaus Golka in:

  22. Search for Rajiv Kumar in:

  23. Search for Jack A Taylor in:

  24. Search for Jose I Mayordomo in:

  25. Search for Kevin B Jacobs in:

  26. Search for Manolis Kogevinas in:

  27. Search for Amy Hutchinson in:

  28. Search for Zhaoming Wang in:

  29. Search for Yi-Ping Fu in:

  30. Search for Ludmila Prokunina-Olsson in:

  31. Search for Laurie Burdett in:

  32. Search for Meredith Yeager in:

  33. Search for William Wheeler in:

  34. Search for Adonina Tardón in:

  35. Search for Consol Serra in:

  36. Search for Alfredo Carrato in:

  37. Search for Reina García-Closas in:

  38. Search for Josep Lloreta in:

  39. Search for Alison Johnson in:

  40. Search for Molly Schwenn in:

  41. Search for Margaret R Karagas in:

  42. Search for Alan Schned in:

  43. Search for Gerald Andriole in:

  44. Search for Robert Grubb in:

  45. Search for Amanda Black in:

  46. Search for Eric J Jacobs in:

  47. Search for W Ryan Diver in:

  48. Search for Susan M Gapstur in:

  49. Search for Stephanie J Weinstein in:

  50. Search for Jarmo Virtamo in:

  51. Search for Victoria K Cortessis in:

  52. Search for Manuela Gago-Dominguez in:

  53. Search for Malcolm C Pike in:

  54. Search for Mariana C Stern in:

  55. Search for Jian-Min Yuan in:

  56. Search for David J Hunter in:

  57. Search for Monica McGrath in:

  58. Search for Colin P Dinney in:

  59. Search for Bogdan Czerniak in:

  60. Search for Meng Chen in:

  61. Search for Hushan Yang in:

  62. Search for Sita H Vermeulen in:

  63. Search for Katja K Aben in:

  64. Search for J Alfred Witjes in:

  65. Search for Remco R Makkinje in:

  66. Search for Patrick Sulem in:

  67. Search for Soren Besenbacher in:

  68. Search for Kari Stefansson in:

  69. Search for Elio Riboli in:

  70. Search for Paul Brennan in:

  71. Search for Salvatore Panico in:

  72. Search for Carmen Navarro in:

  73. Search for Naomi E Allen in:

  74. Search for H Bas Bueno-de-Mesquita in:

  75. Search for Dimitrios Trichopoulos in:

  76. Search for Neil Caporaso in:

  77. Search for Maria Teresa Landi in:

  78. Search for Federico Canzian in:

  79. Search for Borje Ljungberg in:

  80. Search for Anne Tjonneland in:

  81. Search for Francoise Clavel-Chapelon in:

  82. Search for David T Bishop in:

  83. Search for Mark T W Teo in:

  84. Search for Margaret A Knowles in:

  85. Search for Simonetta Guarrera in:

  86. Search for Silvia Polidoro in:

  87. Search for Fulvio Ricceri in:

  88. Search for Carlotta Sacerdote in:

  89. Search for Alessandra Allione in:

  90. Search for Geraldine Cancel-Tassin in:

  91. Search for Silvia Selinski in:

  92. Search for Jan G Hengstler in:

  93. Search for Holger Dietrich in:

  94. Search for Tony Fletcher in:

  95. Search for Peter Rudnai in:

  96. Search for Eugen Gurzau in:

  97. Search for Kvetoslava Koppova in:

  98. Search for Sophia C E Bolick in:

  99. Search for Ashley Godfrey in:

  100. Search for Zongli Xu in:

  101. Search for José I Sanz-Velez in:

  102. Search for María D García-Prats in:

  103. Search for Manuel Sanchez in:

  104. Search for Gabriel Valdivia in:

  105. Search for Stefano Porru in:

  106. Search for Simone Benhamou in:

  107. Search for Robert N Hoover in:

  108. Search for Joseph F Fraumeni in:

  109. Search for Debra T Silverman in:

  110. Search for Stephen J Chanock in:

Contributions

N.R., M.G.-C., N.C., J.D.F., D.T.S. and S.J.C. organized and designed the study.S.J.C., K.B.J., A.H., Z.W., Y.-P.F., .L.P.-O., L.B., X.W., M.A.T.H., M.C., D.V.D.B., S.G., S.P., R.R.M., I.D.V., T.R., D.T.B., G.C.-T., J.G.H., R.K., S.C.E.B. and A.G. conducted and supervised genotyping of samples.

M.G.-C., N.C., N.R., K.B.J., M.Y., N.M., D.T.S. and S.J.C. contributed to the design and execution of statistical analysis.

M.G.-C., N.R., N.C., N.M., J.D.F., F.X.R., J.F.F., D.T.S. and S.J.C. wrote the first draft of the manuscript.N.R., M.G.-C., N.M., X.W., J.D.F., F.X.R., D.V.D.B., F.X.R., G.M., D.B., M.T., L.A.K., P.V., I.D.V., D.A., M.P.P., T.R., M.A.T.H., A.E.K., O.C., K.G., R.K., J.A.T., J.I.M., M.K., A.T., C.S., A.C., R.G.-C., J.L., A.J., M.S., M.R.K., A.S., G.A., R.G., A.B., E.J.J., W.R.D., S.M.G., S.J.W., J.V., V.K.C., M.G.-D., M.C.P., M.C.S., J.-M.Y., D.J.H., M.M., C.P.D., B.C., M.C., H.Y., S.H.V., K.K.A., J.A.W., R.R.M., P.S., S.B., K.S., E.R., P.B., S.P., C.N., N.E.A., H.B.B., D.T., N.C., M.T.L., F.C., B.L., A.T., F.C.-C., D.T.B., M.T.W.T., M.A.K., S.G., S.P., F.R., C.S., A.A., G.C.-T., S.S., J.G.H., H.D., T.F., P.R., E.G., K.K., S.C.E.B., A.G., Z.X., J.I.S.-V., M.D.G.-P., M.S., G.V., S.P., S.B., R.N.H., J.F.F., D.T.S. and S.J.C. conducted the epidemiologic studies and contributed samples to the bladder cancer GWAS and/or replication.

All authors contributed to the writing of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Montserrat Garcia-Closas.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7, Supplementary Tables 1–4 and Supplementary Note

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.687

Further reading