Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

Julius Gudmundsson; Patrick Sulem; Andrei Manolescu; Laufey T. Amundadottir; Daniel Gudbjartsson; Agnar Helgason; Thorunn Rafnar; Jon T. Bergthorsson; Bjarni A. Agnarsson; Adam Baker; Asgeir Sigurdsson; Kristrun R. Benediktsdottir; Margret Jakobsdottir; Jianfeng Xu; Thorarinn Blondal; Jelena Kostic; Jielin Sun; Shyamali Ghosh; Simon N. Stacey; Magali Mouy; Jona Saemundsdottir; Valgerdur M. Backman; Kristleifur Kristjansson; Alejandro Tres; Alan W. Partin; Marjo T. Albers-Akkers; Javier Godino-Ivan Marcos; Patrick C. Walsh; Dorine W. Swinkels; Sebastian Navarrete; Sarah D. Isaacs; Katja K. Aben; Theresa Graif; John Cashy; Manuel Ruiz-Echarri; Kathleen E. Wiley; Brian K. Suarez; J. Alfred Witjes; Mike Frigge; Carole Ober; Eirikur Jonsson; Gudmundur V. Einarsson; Jose I. Mayordomo; Lambertus A. Kiemeney; William B. Isaacs; William J. Catalona; Rosa B. Barkardottir; Jeffrey R. Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson

doi:10.1038/ng1999

Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

Julius Gudmundsson, Patrick Sulem, Andrei Manolescu, Laufey T. Amundadottir, Daniel Gudbjartsson, Agnar Helgason, Thorunn Rafnar, Jon T. Bergthorsson, Bjarni A. Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R. Benediktsdottir, Margret Jakobsdottir, Jianfeng Xu, Thorarinn Blondal, Jelena Kostic, Jielin Sun, Shyamali Ghosh, Simon N. Stacey, Magali MouyJona Saemundsdottir, Valgerdur M. Backman, Kristleifur Kristjansson, Alejandro Tres, Alan W. Partin, Marjo T. Albers-Akkers, Javier Godino-Ivan Marcos, Patrick C. Walsh, Dorine W. Swinkels, Sebastian Navarrete, Sarah D. Isaacs, Katja K. Aben, Theresa Graif, John Cashy, Manuel Ruiz-Echarri, Kathleen E. Wiley, Brian K. Suarez, J. Alfred Witjes, Mike Frigge, Carole Ober, Eirikur Jonsson, Gudmundur V. Einarsson, Jose I. Mayordomo, Lambertus A. Kiemeney, William B. Isaacs, William J. Catalona, Rosa B. Barkardottir, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong^*, Kari Stefansson

^*Corresponding author for this work

Urology

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Abstract

Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Original language	English (US)
Pages (from-to)	631-637
Number of pages	7
Journal	Nature Genetics
Volume	39
Issue number	5
DOIs	https://doi.org/10.1038/ng1999
State	Published - May 2007

ASJC Scopus subject areas

Genetics

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10.1038/ng1999

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Gudmundsson, J., Sulem, P., Manolescu, A., Amundadottir, L. T., Gudbjartsson, D., Helgason, A., Rafnar, T., Bergthorsson, J. T., Agnarsson, B. A., Baker, A., Sigurdsson, A., Benediktsdottir, K. R., Jakobsdottir, M., Xu, J., Blondal, T., Kostic, J., Sun, J., Ghosh, S., Stacey, S. N., ... Stefansson, K. (2007). Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nature Genetics, 39(5), 631-637. https://doi.org/10.1038/ng1999

@article{fdbc88d929db4402b2ed7bdacb777884,

title = "Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24",

abstract = "Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.",

author = "Julius Gudmundsson and Patrick Sulem and Andrei Manolescu and Amundadottir, {Laufey T.} and Daniel Gudbjartsson and Agnar Helgason and Thorunn Rafnar and Bergthorsson, {Jon T.} and Agnarsson, {Bjarni A.} and Adam Baker and Asgeir Sigurdsson and Benediktsdottir, {Kristrun R.} and Margret Jakobsdottir and Jianfeng Xu and Thorarinn Blondal and Jelena Kostic and Jielin Sun and Shyamali Ghosh and Stacey, {Simon N.} and Magali Mouy and Jona Saemundsdottir and Backman, {Valgerdur M.} and Kristleifur Kristjansson and Alejandro Tres and Partin, {Alan W.} and Albers-Akkers, {Marjo T.} and {Godino-Ivan Marcos}, Javier and Walsh, {Patrick C.} and Swinkels, {Dorine W.} and Sebastian Navarrete and Isaacs, {Sarah D.} and Aben, {Katja K.} and Theresa Graif and John Cashy and Manuel Ruiz-Echarri and Wiley, {Kathleen E.} and Suarez, {Brian K.} and Witjes, {J. Alfred} and Mike Frigge and Carole Ober and Eirikur Jonsson and Einarsson, {Gudmundur V.} and Mayordomo, {Jose I.} and Kiemeney, {Lambertus A.} and Isaacs, {William B.} and Catalona, {William J.} and Barkardottir, {Rosa B.} and Gulcher, {Jeffrey R.} and Unnur Thorsteinsdottir and Augustine Kong and Kari Stefansson",

note = "Funding Information: We thank the patients and their family members whose contributions made this work possible. We also thank the nurses at Noatun (deCODE{\textquoteright}s sample recruitment center), personnel at the deCODE core facilities and at the Department of Pathology at Landspitali University Hospital for their hard work and enthusiasm. We acknowledge M. Gielzak, G. Yan and J. Sauvageot (Johns Hopkins Hospital) for their assistance and W.T. Gerrard, M. Duhon, John and Jennifer Chalsty and D. Koch (also at Johns Hopkins Hospital) for their support. We also thank participants and clinicians at the Northwestern University, the University of Chicago, Johns Hopkins Hospital, the Radboud University Nijmegen Medical Centre and the Oncology Department of the Zaragoza Hospital. This project was funded in part by contract number 018827 (Polygene) from the 6th Framework Program of the European Union and by Department of Defense Congressionally Directed Medical Research Program grant W81XWH-05-1-0074.",

year = "2007",

month = may,

doi = "10.1038/ng1999",

language = "English (US)",

volume = "39",

pages = "631--637",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

Gudmundsson, J, Sulem, P, Manolescu, A, Amundadottir, LT, Gudbjartsson, D, Helgason, A, Rafnar, T, Bergthorsson, JT, Agnarsson, BA, Baker, A, Sigurdsson, A, Benediktsdottir, KR, Jakobsdottir, M, Xu, J, Blondal, T, Kostic, J, Sun, J, Ghosh, S, Stacey, SN, Mouy, M, Saemundsdottir, J, Backman, VM, Kristjansson, K, Tres, A, Partin, AW, Albers-Akkers, MT, Godino-Ivan Marcos, J, Walsh, PC, Swinkels, DW, Navarrete, S, Isaacs, SD, Aben, KK, Graif, T, Cashy, J, Ruiz-Echarri, M, Wiley, KE, Suarez, BK, Witjes, JA, Frigge, M, Ober, C, Jonsson, E, Einarsson, GV, Mayordomo, JI, Kiemeney, LA, Isaacs, WB, Catalona, WJ, Barkardottir, RB, Gulcher, JR, Thorsteinsdottir, U, Kong, A & Stefansson, K 2007, 'Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24', Nature Genetics, vol. 39, no. 5, pp. 631-637. https://doi.org/10.1038/ng1999

TY - JOUR

T1 - Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

AU - Gudmundsson, Julius

AU - Sulem, Patrick

AU - Manolescu, Andrei

AU - Amundadottir, Laufey T.

AU - Gudbjartsson, Daniel

AU - Helgason, Agnar

AU - Rafnar, Thorunn

AU - Bergthorsson, Jon T.

AU - Agnarsson, Bjarni A.

AU - Baker, Adam

AU - Sigurdsson, Asgeir

AU - Benediktsdottir, Kristrun R.

AU - Jakobsdottir, Margret

AU - Xu, Jianfeng

AU - Blondal, Thorarinn

AU - Kostic, Jelena

AU - Sun, Jielin

AU - Ghosh, Shyamali

AU - Stacey, Simon N.

AU - Mouy, Magali

AU - Saemundsdottir, Jona

AU - Backman, Valgerdur M.

AU - Kristjansson, Kristleifur

AU - Tres, Alejandro

AU - Partin, Alan W.

AU - Albers-Akkers, Marjo T.

AU - Godino-Ivan Marcos, Javier

AU - Walsh, Patrick C.

AU - Swinkels, Dorine W.

AU - Navarrete, Sebastian

AU - Isaacs, Sarah D.

AU - Aben, Katja K.

AU - Graif, Theresa

AU - Cashy, John

AU - Ruiz-Echarri, Manuel

AU - Wiley, Kathleen E.

AU - Suarez, Brian K.

AU - Witjes, J. Alfred

AU - Frigge, Mike

AU - Ober, Carole

AU - Jonsson, Eirikur

AU - Einarsson, Gudmundur V.

AU - Mayordomo, Jose I.

AU - Kiemeney, Lambertus A.

AU - Isaacs, William B.

AU - Catalona, William J.

AU - Barkardottir, Rosa B.

AU - Gulcher, Jeffrey R.

AU - Thorsteinsdottir, Unnur

AU - Kong, Augustine

AU - Stefansson, Kari

N1 - Funding Information: We thank the patients and their family members whose contributions made this work possible. We also thank the nurses at Noatun (deCODE’s sample recruitment center), personnel at the deCODE core facilities and at the Department of Pathology at Landspitali University Hospital for their hard work and enthusiasm. We acknowledge M. Gielzak, G. Yan and J. Sauvageot (Johns Hopkins Hospital) for their assistance and W.T. Gerrard, M. Duhon, John and Jennifer Chalsty and D. Koch (also at Johns Hopkins Hospital) for their support. We also thank participants and clinicians at the Northwestern University, the University of Chicago, Johns Hopkins Hospital, the Radboud University Nijmegen Medical Centre and the Oncology Department of the Zaragoza Hospital. This project was funded in part by contract number 018827 (Polygene) from the 6th Framework Program of the European Union and by Department of Defense Congressionally Directed Medical Research Program grant W81XWH-05-1-0074.

PY - 2007/5

Y1 - 2007/5

N2 - Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

AB - Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

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U2 - 10.1038/ng1999

DO - 10.1038/ng1999

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AN - SCOPUS:34247563453

SN - 1061-4036

VL - 39

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EP - 637

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

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