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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 (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10??) and rs7579899 (P = 2.3 × 10??), 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?¹?). 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??). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

SUBMITTER: Purdue MP 

PROVIDER: S-EPMC3049257 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20101205 1

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 EPAS  ...[more]

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