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

Abstract

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.

Wiek zachorowania i płeć jako czynniki modyfikujące związek polimorfizmów zlokalizowanych na chromosomie 9q22 i 14q13 z rakiem brodawkowatym tarczycy

“…LD between rs965513 and rs1867277 is significantly weaker in populations of African or Asian ancestry [20], which is not surprising, since the LD block structure may be different in individuals of different ancestry [22]. In our study we observed LD between rs965513, rs1867277, and rs1443434; however, that between rs1867277 and rs1443434 was the strongest.…”

“…lysed and confirmed in Caucasians [18][19][20], whereas rs944289 was associated with PTC in Asians, Europeans, and Americans [21] .…”

rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer

“…Kang J. et al included 8 studies corresponding to 2,085 cases and 10,341 controls [31]. Zhuang Y. et al included 13 studies involving 8491 cases, 103,218 control and 629 family members [32]. Ai L et al included 6 studies and a total of 52,363 individuals (5,193 cases vs. 47,170 controls) [33].…”

“…Moreover, we evaluated the risk of thyroid cancer with rs965513 under several genetic models including the additive, recessive, dominant and homozygous models, to assess the increased levels of PTC risk under different genotypes. Zhuang et al evaluated the allelic, dominant and recessive models [32]. Ai L et al performed meta-analysis using additive model [33].…”

Association between FOXP3, FOXE1 Gene Polymorphisms and Risk of Differentiated Thyroid Cancer in Chinese Han Population

“…Besides medullary carcinoma, most of thyroid cancer originated in the follicular epithelial cells. The differentiated thyroid cancers (DTC) include papillary (PTC, 80-90% of cases) and follicular (FTC, 10% of cases) subtypes and their etiology are still not very clear [2]. It is no doubt that thyroid carcinoma is the result of interaction between genetic and environmental factors [3,4].…”