TY - JOUR
T1 - Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer
AU - Henrion, Marc Y.R.
AU - Purdue, Mark P.
AU - Scelo, Ghislaine
AU - Broderick, Peter
AU - Frampton, Matthew
AU - Ritchie, Alastair
AU - Meade, Angela
AU - Li, Peng
AU - McKay, James
AU - Johansson, Mattias
AU - Lathrop, Mark
AU - Larkin, James
AU - Rothman, Nathaniel
AU - Wang, Zhaoming
AU - Chow, Wong Ho
AU - Stevens, Victoria L.
AU - Diver, W. Ryan
AU - Albanes, Demetrius
AU - Virtamo, Jarmo
AU - Brennan, Paul
AU - Eisen, Timothy
AU - Chanock, Stephen
AU - Houlston, Richard S.
N1 - Funding Information:
Zhaoming Wang is employed by Leidos Biomedical Research Inc., a US government contractor. Timothy Eisen is Chief Investigator of SORCE and has received research support form Bayer, GlaxoSmithKline, Pfizer and AstraZeneca, has taken part and been compensated for advisory boards for GlaxoSmithKline, Aveo and Astellas and is currently on leave of absence from the University of Cambridge to work as Chief Clinician Scientist at AstraZeneca. SORCE, though coordinated by the Medical Research Council (MRC) Clinical Trials Unit (CTU) at UCL and funded principally by the MRC CTU at UCL and Cancer Research UK, has been funded partially by an educational grant from a commercial source, Bayer. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015, Public Library of Science. All rights reserved.
PY - 2015/3/31
Y1 - 2015/3/31
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0122589
DO - 10.1371/journal.pone.0122589
M3 - Article
C2 - 25826619
AN - SCOPUS:84926640535
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 3
M1 - e0122589
ER -