Common genetic variants on FOXE1 contributes to thyroid cancer susceptibility: evidence based on 16 studies

Genome-wide association studies have identified polymorphisms at chromosome 9q22.23 as a new thyroid cancer (TC) susceptibility locus in populations of European descent. Since then, the relationship between three common variations (rs965513, rs1867277, and rs71369530) of FOXE1 and TC has been reported in various ethnic groups; however, the results have been inconclusive. To derive a more precise estimation of the relationship as well as to quantify the between-study heterogeneity and potential bias, a meta-analysis including 120,258 individuals from 16 studies was performed. An overall random-effect per-allele odds ratio (OR) of 1.74 (95 % confidence interval (95 % CI), 1.62-1.86, P<10(-5)) and 1.62 (95 % CI, 1.50-1.76, P<10(-5)) was found for the rs965513 and rs1867277 polymorphisms, respectively. In addition, we also detected significant association of FOXE1 polyalanine tract (rs71369530) with TC risk (OR=2.01; 95 % CI, 1.66-2.44, P<10(-5)). Significant associations were also detected under dominant and recessive genetic models. In the subgroup analysis by ethnicity, significantly increased risks were found for the rs965513 polymorphism among Caucasians (OR=1.79; 95 % CI, 1.69-1.91, P<10(-5)) and Asians (OR=1.42; 95 % CI, 1.12-1.81, P=0.004). Ethnicity was identified as a potential source of between-study heterogeneity for rs965513. When stratified by sample size, study design, histological types of TC, and radiation exposure status, significantly increased risks were found for the rs965513 polymorphism. This meta-analysis demonstrated that the three common variations on FOXE1 is a risk factor associated with increased TC susceptibility, but these associations vary in different ethnic populations.