Closa A, Cordero D, Sanz-Pamplona R, Solé X, Crous-Bou M, Paré-Brunet L, Berenguer A, Guino E, Lopez-Doriga A, Guardiola J, Biondo S, Salazar R, Moreno V.
Carcinogenesis. 2014 Sep;35(9):2039-46. doi: 10.1093/carcin/bgu092.
PMID: 24760461
Abstract
In this study we aim to identify the genes responsible for colorectal cancer (CRC) risk behind the loci identified in genome-wide association studies (GWAS). These genes may be candidate targets for developing new strategies for prevention or therapy. We analyzed the association of genotypes for 26 GWAS SNPs with the expression of genes within 2Mb (cis-eQTLs). Affymetrix Human Genome U219 expression arrays were used to assess gene expression in two series of samples, one of healthy colonic mucosa (n=47) and other of normal mucosa adjacent to colon cancer (n=97, total 144). Paired tumor tissues (n=97) were also analyzed, but did not provide additional findings. Partial Pearson correlation (r), adjusted for sample type, was used for the analysis. We have found Bonferroni-significant cis-eQTLs in three loci: rs3802842 in 11q23.1 associated to C11orf53, COLCA1 (C11orf92) and COLCA2 (C11orf93) (r=0.60); rs7136702 in 12q13.12 associated to DIP2B (r=0.63); and rs5934683 in Xp22.3 associated to SHROOM2 and GPR143 (r=0.47). For loci in chromosomes 11 and 12, we have found other SNPs in LD that are more strongly associated with the expression of the identified genes and are better functional candidates: rs7130173 for 11q23.1 (r=0.66) and rs61927768 for 12q13.12 (r=0.86). These SNPs are located in DNA regions that may harbor enhancers or transcription factor binding sites. The analysis of trans-eQTLs has identified additional genes in these loci that may have common regulatory mechanisms as shown by the analysis of protein-protein interaction networks.
