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

Purdue, M. P.; Johansson, M.; Zelenika, D.; Toro, J. R.; Scelo, G.; Moore, L. E.; Prokhortchouk, E.; Wu, X.; Kiemeney, L. A.; Gaborieau, V.; Jacobs, K. B.; Chow, W. -H.; 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, J. S.; Davis, F. G.; Schwartz, K. L.; Banks, R. E.; Selby, P. J.; Harnden, P.; Berg, C. D.; Hsing, A. W.; Grubb, R. L.; Boeing, H.; Vineis, P.; Clavel-Chapelon, F.; Palli, D.; Tumino, R.; Krogh, V.; Panico, S.; Duell, E. J.; Quiós, J. R.; Sanchez, M. -J.; Navarro, C.; Ardanaz, E.; Dorronsoro, M.; Khaw, K. -T.; Allen, N. E.; Bueno-De-Mesquita, H. B.; Peeters, P. H. M.; Trichopoulos, D.; Linseisen, J.; Ljungberg, B.; Overvad, K.; Tjønneland, A.; Romieu, I.; Riboli, E.; Mukeria, A.; Shangina, O.; Stevens, V. L.; Thun, M. J.; Diver, W. R.; Gapstur, S. M.; Pharoah, P. D.; Easton, D. F.; Albanes, D.; Weinstein, S. J.; Virtamo, J.; Vatten, L.; Hveem, K.; Njølstad, I.; Tell, G. S.; Stoltenberg, C.; Kumar, Rajat; Koppova, K.; Cussenot, O.; Benhamou, S.; Oosterwijk, E.; Vermeulen, S. H.; Aben, K. K. H.; Van Der Marel, S. L.; Ye, Y.; Wood, C. G.; Pu, X.; Mazur, A. M.; Boulygina, E. S.; Chekanov, N. N.; Foglio, M.; Lechner, D.; Gut, I.; Heath, S.; Blanche, H.; Hutchinson, A.; Thomas, G.; Wang, Z.; Yeager, M.; Fraumeni Jr., J. F.; Skryabin, K. G.; Mckay, J. D.; Rothman, N.; Chanock, S. J.; Lathrop, M.; Brennan, P.

doi:10.1038/ng.723

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. © 2011 Nature America, Inc. All rights reserved.

Purdue, M., Johansson, M., Zelenika, D., Toro, J., Scelo, G., Moore, L., et al. (2011). Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. NATURE GENETICS, 43(1), 60-65 [10.1038/ng.723].