Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer

Abstract

Genome-wide association studies (GWASs) of renal cell cancer (RCC) have identified four susceptibility loci thus far. To identify an additional RCC common susceptibility locus, we conducted a GWAS and performed a meta-analysis with published GWASs (totalling 2215 cases and 8566 controls of European background) and followed up the most significant association signals [nine single nucleotide polymorphisms (SNPs) in eight genomic regions] in 3739 cases and 8786 controls. A combined analysis identified a novel susceptibility locus mapping to 2q22.3 marked by rs12105918 (P = 1.80 × 10(-8); odds ratio 1.29, 95% CI: 1.18-1.41). The signal localizes to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2). Our findings suggest that genetic variation in ZEB2 influences the risk of RCC. This finding provides further insights into the genetic and biological basis of inherited genetic susceptibility to RCC.

Figure 1.

Regional plot of association results and recombination rates for the 2q22.3 risk locus. Association results of genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates. −log₁₀P values (y-axis) of the SNPs are shown according to their chromosomal positions (x-axis). rs12105918 in the combined analysis is denoted by a large triangle. The colour intensity of each symbol reflects the extent of LD with rs12105918: white (r² = 0) through to dark red (r² = 1.0), with r² estimated from the UK control samples. Genetic recombination rates (cM/Mb), estimated using 1000 Genomes Pilot 1 CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 37 of the human genome. Also shown are the relative positions of genes and transcripts mapping to each region of association. Genes have been redrawn to show the relative positions; therefore, the maps are not to physical scale.