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

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 (r2 = 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.

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

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