Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer

Marc Y.R. Henrion, Mark P. Purdue, Ghislaine Scelo, Peter Broderick, Matthew Frampton, Alastair Ritchie, Angela Meade, Peng Li, James McKay, Mattias Johansson, Mark Lathrop, James Larkin, Nathaniel Rothman, Zhaoming Wang, Wong Ho Chow, Victoria L. Stevens, W. Ryan Diver, Demetrius Albanes, Jarmo Virtamo, Paul BrennanTimothy Eisen, Stephen Chanock, Richard S. Houlston

Research output: Contribution to journalArticle

Abstract

So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30×10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined=2.73×10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.

Original languageEnglish (US)
Article numbere0122589
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 31 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Henrion, M. Y. R., Purdue, M. P., Scelo, G., Broderick, P., Frampton, M., Ritchie, A., Meade, A., Li, P., McKay, J., Johansson, M., Lathrop, M., Larkin, J., Rothman, N., Wang, Z., Chow, W. H., Stevens, V. L., Diver, W. R., Albanes, D., Virtamo, J., ... Houlston, R. S. (2015). Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer. PloS one, 10(3), [e0122589]. https://doi.org/10.1371/journal.pone.0122589