Association of the 15q25 and 5p15 lung cancer susceptibility regions with gene expression in lung tumour tissue
A partir des données de deux études indépendantes incluant 312 patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue l'association entre 12 variants génétiques situés sur les chromosomes 15q25 et 5p15, l'expression des gènes correspondant dans les cellules tumorales et le risque de développer la maladie
Background: Genome-wide association studies have identified two independent lung cancer susceptibility loci at chromosome 15q25 and one locus at 5p15. We examined the association of genetic variants in these regions with gene expression in lung tumor tissue, in an effort to elucidate carcinogeneic mechanisms by which these variants influence lung cancer risk. Methods: We used data from two independent studies of non-small cell lung cancer patients: the JBR.10 clinical trial (n=131) and a University Health Network (UHN) patient sample in Toronto (n=181). We genotyped seven 15q25 and five 5p15 variants and examined their association with expression profiles of genes in the corresponding regions, measured by Affymetrix HG-U133A. Results: The minor allele (C) of a variant representing one of the two loci at 15q25 (rs2036534) was associated with increased IREB2 (iron-responsive element binding protein 2) expression in both studies (JBR.10 P=0.042; UHN P=0.002). An FDR≤0.05 in the UHN sample increased our confidence in this association. The association appears to be more prominent among lung adenocarcinoma patients. We did not detect an association between genotype and expression profile for the other 15q25 locus or for 5p15 variants. Conclusions: In contrast to previous studies that indicate 15q25 variants are associated with lung cancer risk through an effect on smoking behaviour, our results suggest these variants may influence risk through a second mechanism, involving modulation of IREB2 expression. Impact: This finding expands on potential mechanisms through which 15q25 variants influence lung cancer risk and may have implications for future research on chemoprevention strategies.