Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

Mark P. Purdue, Mattias Johansson, Diana Zelenika, Jorge R. Toro, Ghislaine Scelo, Lee E. Moore, Egor Prokhortchouk, Xifeng Wu, Lambertus A. Kiemeney, Valerie Gaborieau, Kevin B. Jacobs, Wong Ho Chow, David Zaridze, Vsevolod Matveev, Jan Lubinski, Joanna Trubicka, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, P. Rudnai, Eleonora FabianovaAlexandru Bucur, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Paolo Boffetta, Joanne S. Colt, Faith G. Davis, Kendra L. Schwartz, Rosamonde E. Banks, Peter J. Selby, Patricia Harnden, Christine D. Berg, Ann W. Hsing, Robert L. Grubb, Heiner Boeing, Paolo Vineis, Franc̃oise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Eric J. Duell, José Ramón Quiós, Maria José Sanchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Kay Tee Khaw, Naomi E. Allen, H. Bas Bueno-De-Mesquita, Petra H M Peeters, Dimitrios Trichopoulos, Jakob Linseisen, Börje Ljungberg, Kim Overvad, Anne Tjønneland, Isabelle Romieu, Elio Riboli, Anush Mukeria, Oxana Shangina, Victoria L. Stevens, Michael J. Thun, W. Ryan Diver, Susan M. Gapstur, Paul D. Pharoah, Douglas F. Easton, Demetrius Albanes, Stephanie J. Weinstein, Jarmo Virtamo, Lars Vatten, Kristian Hveem, Inger Njølstad, Grethe S. Tell, Camilla Stoltenberg, Rajiv Kumar, Kvetoslava Koppova, Olivier Cussenot, Simone Benhamou, Egbert Oosterwijk, Sita H. Vermeulen, Katja K H Aben, Saskia L. Van Der Marel, Yuanqing Ye, Christopher G. Wood, Xia Pu, Alexander M. Mazur, Eugenia S. Boulygina, Nikolai N. Chekanov, Mario Foglio, Doris Lechner, Ivo Gut, Simon Heath, Hélène Blanche, Amy Hutchinson, Gilles Thomas, Zhaoming Wang, Meredith Yeager, Joseph F. Fraumeni, Konstantin G. Skryabin, James D. McKay, Nathaniel Rothman, Stephen J. Chanock, Mark Lathrop, Paul Brennan

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r 2 = 0.99 in controls), rs11894252 (P = 1.8 ×- 10-8) and rs7579899 (P = 2.3 ×- 10-9), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 ×- 10-14). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 ×- 10 -8). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

Original languageEnglish
Pages (from-to)60-65
Number of pages6
JournalNature Genetics
Volume43
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Genome-Wide Association Study
Renal Cell Carcinoma
Class B Scavenger Receptors
Genes
Single Nucleotide Polymorphism
Transcription Factors
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Purdue, M. P., Johansson, M., Zelenika, D., Toro, J. R., Scelo, G., Moore, L. E., ... Brennan, P. (2011). Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nature Genetics, 43(1), 60-65. https://doi.org/10.1038/ng.723

Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. / Purdue, Mark P.; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R.; Scelo, Ghislaine; Moore, Lee E.; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A.; Gaborieau, Valerie; Jacobs, Kevin B.; Chow, Wong Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, P.; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S.; Davis, Faith G.; Schwartz, Kendra L.; Banks, Rosamonde E.; Selby, Peter J.; Harnden, Patricia; Berg, Christine D.; Hsing, Ann W.; Grubb, Robert L.; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Franc̃oise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J.; Quiós, José Ramón; Sanchez, Maria José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay Tee; Allen, Naomi E.; Bueno-De-Mesquita, H. Bas; Peeters, Petra H M; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Pharoah, Paul D.; Easton, Douglas F.; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njølstad, Inger; Tell, Grethe S.; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H.; Aben, Katja K H; Van Der Marel, Saskia L.; Ye, Yuanqing; Wood, Christopher G.; Pu, Xia; Mazur, Alexander M.; Boulygina, Eugenia S.; Chekanov, Nikolai N.; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Hélène; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F.; Skryabin, Konstantin G.; McKay, James D.; Rothman, Nathaniel; Chanock, Stephen J.; Lathrop, Mark; Brennan, Paul.

In: Nature Genetics, Vol. 43, No. 1, 01.2011, p. 60-65.

Research output: Contribution to journalArticle

Purdue, MP, Johansson, M, Zelenika, D, Toro, JR, Scelo, G, Moore, LE, Prokhortchouk, E, Wu, X, Kiemeney, LA, Gaborieau, V, Jacobs, KB, Chow, WH, Zaridze, D, Matveev, V, Lubinski, J, Trubicka, J, Szeszenia-Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Foretova, L, Janout, V, Boffetta, P, Colt, JS, Davis, FG, Schwartz, KL, Banks, RE, Selby, PJ, Harnden, P, Berg, CD, Hsing, AW, Grubb, RL, Boeing, H, Vineis, P, Clavel-Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, S, Duell, EJ, Quiós, JR, Sanchez, MJ, Navarro, C, Ardanaz, E, Dorronsoro, M, Khaw, KT, Allen, NE, Bueno-De-Mesquita, HB, Peeters, PHM, Trichopoulos, D, Linseisen, J, Ljungberg, B, Overvad, K, Tjønneland, A, Romieu, I, Riboli, E, Mukeria, A, Shangina, O, Stevens, VL, Thun, MJ, Diver, WR, Gapstur, SM, Pharoah, PD, Easton, DF, Albanes, D, Weinstein, SJ, Virtamo, J, Vatten, L, Hveem, K, Njølstad, I, Tell, GS, Stoltenberg, C, Kumar, R, Koppova, K, Cussenot, O, Benhamou, S, Oosterwijk, E, Vermeulen, SH, Aben, KKH, Van Der Marel, SL, Ye, Y, Wood, CG, Pu, X, Mazur, AM, Boulygina, ES, Chekanov, NN, Foglio, M, Lechner, D, Gut, I, Heath, S, Blanche, H, Hutchinson, A, Thomas, G, Wang, Z, Yeager, M, Fraumeni, JF, Skryabin, KG, McKay, JD, Rothman, N, Chanock, SJ, Lathrop, M & Brennan, P 2011, 'Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3', Nature Genetics, vol. 43, no. 1, pp. 60-65. https://doi.org/10.1038/ng.723
Purdue, Mark P. ; Johansson, Mattias ; Zelenika, Diana ; Toro, Jorge R. ; Scelo, Ghislaine ; Moore, Lee E. ; Prokhortchouk, Egor ; Wu, Xifeng ; Kiemeney, Lambertus A. ; Gaborieau, Valerie ; Jacobs, Kevin B. ; Chow, Wong Ho ; Zaridze, David ; Matveev, Vsevolod ; Lubinski, Jan ; Trubicka, Joanna ; Szeszenia-Dabrowska, Neonila ; Lissowska, Jolanta ; Rudnai, P. ; Fabianova, Eleonora ; Bucur, Alexandru ; Bencko, Vladimir ; Foretova, Lenka ; Janout, Vladimir ; Boffetta, Paolo ; Colt, Joanne S. ; Davis, Faith G. ; Schwartz, Kendra L. ; Banks, Rosamonde E. ; Selby, Peter J. ; Harnden, Patricia ; Berg, Christine D. ; Hsing, Ann W. ; Grubb, Robert L. ; Boeing, Heiner ; Vineis, Paolo ; Clavel-Chapelon, Franc̃oise ; Palli, Domenico ; Tumino, Rosario ; Krogh, Vittorio ; Panico, Salvatore ; Duell, Eric J. ; Quiós, José Ramón ; Sanchez, Maria José ; Navarro, Carmen ; Ardanaz, Eva ; Dorronsoro, Miren ; Khaw, Kay Tee ; Allen, Naomi E. ; Bueno-De-Mesquita, H. Bas ; Peeters, Petra H M ; Trichopoulos, Dimitrios ; Linseisen, Jakob ; Ljungberg, Börje ; Overvad, Kim ; Tjønneland, Anne ; Romieu, Isabelle ; Riboli, Elio ; Mukeria, Anush ; Shangina, Oxana ; Stevens, Victoria L. ; Thun, Michael J. ; Diver, W. Ryan ; Gapstur, Susan M. ; Pharoah, Paul D. ; Easton, Douglas F. ; Albanes, Demetrius ; Weinstein, Stephanie J. ; Virtamo, Jarmo ; Vatten, Lars ; Hveem, Kristian ; Njølstad, Inger ; Tell, Grethe S. ; Stoltenberg, Camilla ; Kumar, Rajiv ; Koppova, Kvetoslava ; Cussenot, Olivier ; Benhamou, Simone ; Oosterwijk, Egbert ; Vermeulen, Sita H. ; Aben, Katja K H ; Van Der Marel, Saskia L. ; Ye, Yuanqing ; Wood, Christopher G. ; Pu, Xia ; Mazur, Alexander M. ; Boulygina, Eugenia S. ; Chekanov, Nikolai N. ; Foglio, Mario ; Lechner, Doris ; Gut, Ivo ; Heath, Simon ; Blanche, Hélène ; Hutchinson, Amy ; Thomas, Gilles ; Wang, Zhaoming ; Yeager, Meredith ; Fraumeni, Joseph F. ; Skryabin, Konstantin G. ; McKay, James D. ; Rothman, Nathaniel ; Chanock, Stephen J. ; Lathrop, Mark ; Brennan, Paul. / Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. In: Nature Genetics. 2011 ; Vol. 43, No. 1. pp. 60-65.
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title = "Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3",
abstract = "We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r 2 = 0.99 in controls), rs11894252 (P = 1.8 ×- 10-8) and rs7579899 (P = 2.3 ×- 10-9), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 ×- 10-14). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 ×- 10 -8). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.",
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T1 - Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

AU - Purdue, Mark P.

AU - Johansson, Mattias

AU - Zelenika, Diana

AU - Toro, Jorge R.

AU - Scelo, Ghislaine

AU - Moore, Lee E.

AU - Prokhortchouk, Egor

AU - Wu, Xifeng

AU - Kiemeney, Lambertus A.

AU - Gaborieau, Valerie

AU - Jacobs, Kevin B.

AU - Chow, Wong Ho

AU - Zaridze, David

AU - Matveev, Vsevolod

AU - Lubinski, Jan

AU - Trubicka, Joanna

AU - Szeszenia-Dabrowska, Neonila

AU - Lissowska, Jolanta

AU - Rudnai, P.

AU - Fabianova, Eleonora

AU - Bucur, Alexandru

AU - Bencko, Vladimir

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Boffetta, Paolo

AU - Colt, Joanne S.

AU - Davis, Faith G.

AU - Schwartz, Kendra L.

AU - Banks, Rosamonde E.

AU - Selby, Peter J.

AU - Harnden, Patricia

AU - Berg, Christine D.

AU - Hsing, Ann W.

AU - Grubb, Robert L.

AU - Boeing, Heiner

AU - Vineis, Paolo

AU - Clavel-Chapelon, Franc̃oise

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Krogh, Vittorio

AU - Panico, Salvatore

AU - Duell, Eric J.

AU - Quiós, José Ramón

AU - Sanchez, Maria José

AU - Navarro, Carmen

AU - Ardanaz, Eva

AU - Dorronsoro, Miren

AU - Khaw, Kay Tee

AU - Allen, Naomi E.

AU - Bueno-De-Mesquita, H. Bas

AU - Peeters, Petra H M

AU - Trichopoulos, Dimitrios

AU - Linseisen, Jakob

AU - Ljungberg, Börje

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Romieu, Isabelle

AU - Riboli, Elio

AU - Mukeria, Anush

AU - Shangina, Oxana

AU - Stevens, Victoria L.

AU - Thun, Michael J.

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Pharoah, Paul D.

AU - Easton, Douglas F.

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Vatten, Lars

AU - Hveem, Kristian

AU - Njølstad, Inger

AU - Tell, Grethe S.

AU - Stoltenberg, Camilla

AU - Kumar, Rajiv

AU - Koppova, Kvetoslava

AU - Cussenot, Olivier

AU - Benhamou, Simone

AU - Oosterwijk, Egbert

AU - Vermeulen, Sita H.

AU - Aben, Katja K H

AU - Van Der Marel, Saskia L.

AU - Ye, Yuanqing

AU - Wood, Christopher G.

AU - Pu, Xia

AU - Mazur, Alexander M.

AU - Boulygina, Eugenia S.

AU - Chekanov, Nikolai N.

AU - Foglio, Mario

AU - Lechner, Doris

AU - Gut, Ivo

AU - Heath, Simon

AU - Blanche, Hélène

AU - Hutchinson, Amy

AU - Thomas, Gilles

AU - Wang, Zhaoming

AU - Yeager, Meredith

AU - Fraumeni, Joseph F.

AU - Skryabin, Konstantin G.

AU - McKay, James D.

AU - Rothman, Nathaniel

AU - Chanock, Stephen J.

AU - Lathrop, Mark

AU - Brennan, Paul

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N2 - We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r 2 = 0.99 in controls), rs11894252 (P = 1.8 ×- 10-8) and rs7579899 (P = 2.3 ×- 10-9), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 ×- 10-14). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 ×- 10 -8). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

AB - We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r 2 = 0.99 in controls), rs11894252 (P = 1.8 ×- 10-8) and rs7579899 (P = 2.3 ×- 10-9), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 ×- 10-14). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 ×- 10 -8). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

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