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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 × 10−8) 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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Figure 1: Association results, recombination and linkage disequilibrium plots for regions below genome-wide significance (2p21 and 11q13.3) and a region with a promising association (12q24.31) to RCC susceptibility.
Figure 2: Forest plots for three SNPs showing significant or promising association to RCC susceptibility.

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Acknowledgements

The authors thank all of the participants who took part in this research and the funders and support staff who made this study possible. Funding for the genome-wide genotyping was provided by the French Institut National du Cancer (INCa) for those studies coordinated by IARC/CNG, and by the intramural research program of the National Cancer Institute (NCI), US National Institutes of Health (NIH) for those studies coordinated by the NCI. Additional acknowledgments can be found in the Supplementary Note.

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M.P.P., M.J., J.R.T., G.S., L.E.M., V.G., W.-H.C., J.D.M., N.R., S.J.C. and P. Brennan contributed to the design and execution of the overall study. M.P.P., M.J., J.R.T., G.S., L.E.M., L.A.K., X.W., V.G., K.B.J., J.D.M., N.R., S.J.C. and P. Brennan contributed to the statistical analyses. M.P.P., M.J., S.J.C. and P. Brennan wrote the first draft of the manuscript. D. Zelenika, E.P., L.A.K., X.W., K.B.J., S.H.V., S.L.v.d.M., Y.Y., A.M.M., E.S.B., N.N.C., M.F., D.L., I.G., S.H., H. Blanche, A.H., G.S.T., Z.W., M.Y., K.G.S., S.J.C. and M.L. supervised or conducted the genotyping. The remaining authors conducted the epidemiologic studies and contributed samples to the GWAS and/or replication studies. All authors contributed to the writing of the manuscript.

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Correspondence to Stephen J Chanock or Paul Brennan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1, 3 and 4, Supplementary Figures 1–3 and Supplementary Note (PDF 677 kb)

Supplementary Table 2

Association results for SNPs imputed on 2p21 (EPAS1), 11q13.3, and 12q24.31 (SCARB1), using data from 1000 Genomes as scaffold (XLS 7053 kb)

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Purdue, M., Johansson, M., Zelenika, D. et al. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet 43, 60–65 (2011). https://doi.org/10.1038/ng.723

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