Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk
Menée aux Etats-Unis à partir de données portant sur 3 885 patients (1 501 patients atteints d'un adénocarcinome œsophagien et 2 384 patients atteints d'un œsophage de Barrett), cette étude évalue l'association entre 387 polymorphismes à simple nucléotide précédemment identifiés dans des études d'association sur le génome entier et le risque d'adénocarcinome œsophagien
Background: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus (BE). Methods: We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (SNPs) that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 BE) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. Results: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or BE. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. Conclusions: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or BE. Impact: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE.