FOXE1 Association with Differentiated Thyroid Cancer and Its Progression

Abstract

Background: Single nucleotide polymorphisms (SNPs) near thyroid transcription factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated with differentiated thyroid cancer (DTC) in Caucasoid populations. We investigated the role of those SNPs in German patients with DTC and also extended our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL). Methods: Patients with DTC (n = 243; papillary, PTC; follicular, FTC) and healthy controls (HC; n = 270) were analyzed for the rs965513 and rs944289 SNPs. Results: The case-control analysis for rs965513 SNP showed that the genotypes ''AA,'' ''AG,'' and minor allele ''A'' were more frequent in patients with DTC than in HC (pronounced in PTC p genotype = 0.000084, p allele = 0.006 than FTC p genotype = 0.29 and p allele = 0.06). Furthermore, subgroup analysis of the DTC patients stratified for primary tumor stage (T1-T2, T3-T4), the absence or presence of regional lymph node metastases (N0, N1), for distant metastases (M0, M1), as well as for ITL, showed an association of rs965513 with stages T1-T2, T1-T3, N1, and absence of ITL. The NKX2-1 SNP rs944289, however, was not associated with DTC. Conclusion: Our results confirm that the FOXE1 rs965513 SNP confers an increased risk for DTC

Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer

“…8 (4). The association between rs965513 and thyroid cancer risk has been independently confirmed in different populations (5)(6)(7)(8)(9)(10)(11). The association was also observed in familial PTC and in patients with radiation-induced PTC (12)(13)(14)(15).…”

“…To assess SNPs across the 9q22 locus and to identify functional SNPs, as well as additional associated variants that may contribute to PTC predisposition, we performed targeted next-generation sequencing in a gene-poor region of about 167 kb [genomic coordinates chromosome 9: 100455000-100622000 (GRCh37/hg19)] on DNA from 22 patients with PTC, including 10 [AA], 6 [AG], and 6 [GG] genotypes of the lead SNP rs965513. The region contains both coding genes (XPA and FOXE1) that flank the lead SNP.…”

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

“…The association of rs965513 and rs944289 with PTC was analysed by Liyanarachchi et al in cohorts from Poland and the United States [2], with results that are in accordance with our study. The association of rs965513, rs1867277, rs944289, and rs1443434 with PTC has been confirmed in different populations in recent years [8][9][10][11][12][13][14][15][16][17]. Moreover, four meta-analyses concerning the roles of rs965513, rs1867277, and rs944289 in PTC have been published: the association of rs965513 has been confirmed among both Caucasians and Asians, rs1867277 SNP was ana-…”

“…At the same time, Landa et al demonstrated an association between PTC and another SNP located in the 5-untranslated region of the FOXE1 -rs1867277 [4]. However, to date, only a few studies have been performed to assess the association of these SNPs with some clinical features of PTC [5,8,9]. To our knowledge, no study has analysed the mutual interactions between identified SNPs and their association with patient--related factors, like gender and age at PTC diagnosis.…”

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

“…Among all the genetic factors, FOXE1 plays an important role in the morphogenetic process which is regulated by both cell-autonomous and mesoderm-derived mechanisms acting in concert to promote growth and survival of progenitor cells [19,20]. In other studies, the FOXE1 variants were associated with the risk of DTC in some populations, including Spain, Belarusian, Portuguese, et al [7,11,21,22].…”