Genetic variants in DNA repair pathways and risk of upper aerodigestive tract cancers: Combined analysis of data from two genome-wide association studies in European populations
A partir de deux bases de données européennes portant sur 1 945 cas de cancer des voies aérodigestives supérieures et 3 121 témoins, cette étude identifie des polymorphismes à simple nucléotide de gènes impliqués dans la réparation de l'ADN en association avec une susceptibilité aux divers sous-types de la maladie
DNA repair pathways are good candidates for upper aero-digestive tract cancer susceptibility because of their critical role in maintaining genome integrity. We have selected thirteen pathways involved in DNA repair representing 212 autosomal genes. To assess the role of these pathways and their associated genes, two European datasets from the International Head and Neck Cancer Epidemiology consortium were pooled, totaling 1954 cases and 3121 controls, with documented demographic, lifetime alcohol and tobacco consumption information. We applied an innovative approach that tests SNP-sets within DNA repair pathways, and then within genes belonging to the significant pathways. We showed an association between the polymerase pathway and oral cavity/pharynx cancers (p-corrected = 4.45 х 10-2), explained entirely by the association with one SNP, rs1494961 (p = 2.65х10-4), a missense mutation V306I in the second exon of HELQ gene. We also found an association between the cell-cycle regulation pathway and esophagus cancer (p-corrected = 1.48х10-2), explained by three SNPs located within or near CSNK1E gene: rs1534891 (p = 1.27х10-4), rs7289981 (p = 3.37х10-3), and rs13054361 (p = 4.09х10–3). As a first attempt to investigate pathway-level associations, our results suggest a role of specific DNA repair genes/pathways in specific UADT cancer sites.
http://carcin.oxfordjournals.org/content/early/2014/03/21/carcin.bgu075.abstract