Lack of replication of seven pancreatic cancer susceptibility loci identified in two Asian populations
Cette étude montre que sept loci de susceptibilité à l'adénocarcinome canalaire du pancréas, identifiés chez deux populations asiatiques, ne sont pas associés au risque de développer la maladie chez les personnes d'origine européenne (1 299 cas et 2 884 témoins)
Background: Two recent genome-wide association studies (GWAS) of pancreatic ductal adenocarcinoma (PDAC), conducted respectively in a Japanese and in a Chinese population, identified eight novel loci affecting PDAC risk. Methods: We attempted to replicate the novel loci in a series of PDAC and healthy controls of European ancestry in the context of the newly formed PANcreatic Disease ReseArch (PANDoRA) consortium. We genotyped seven single nucleotide polymorphisms (SNPs): rs12413624, rs1547374, rs372883, rs5768709, rs6464375, rs708224, rs9502893 (one SNP identified in the Chinese GWAS is not polymorphic in Caucasians) in 1299 PDAC cases and 2884 controls. We also attempted stratified analysis considering the different stages of the disease and addressed the possible involvement of the selected SNPs on the survival of patients. Results: None of the SNPs were significantly associated with PDAC risk if considering the overall population of the consortium. When stratifying for country of origin we found that in the Polish subgroup the G allele of rs372883 was statistically significantly associated with increased risk (OR=6.40; CI 95% 2.28-17.91). However the sample size of the subgroups was rather small, therefore this result can be due to chance. None of the SNPs was associated with disease progression or survival. Conclusions and Impact: None of the SNPs associated with PDAC risk in two Asian populations were convincingly associated with PDAC risk in individuals of European descent. This study illustrates the importance of evaluation of PDAC risk markers across ethnic groups.