Novel Genome-Wide Association Study–Based Candidate Loci for Differentiated Thyroid Cancer Risk

Figlioli, Gisella; Köhler, Aleksandra; Chen, Bowang; Elisei, Rossella; Romei, Cristina; Cipollini, Monica; Cristaudo, Alfonso; Bambi, Franco; Paolicchi, Elisa; Hoffmann, Per; Herms, Stefan; Kalemba, Michał; Kula, Dorota; Pastor, Susana; Marcos, Ricard; Velázquez, Antonia; Jarząb, Barbara; Landi, Stefano; Hemminki, Kari; Försti, Asta; Gemignani, Federica

doi:10.1210/jc.2014-1734

Cited by 48 publications

(56 citation statements)

References 32 publications

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“…Similarly, no association signal was observed in the genomewide step of this study for other markers identified previously (rs966423 at 2q35 and rs2439302 at 8p12 17 or rs10136427 at 14q24.3 and rs7267944 at 20q12 29 ). As all of these genetic variants were described in a single study, without replication by subsequent studies, they could be associated with the disease in a population-specific manner.…”

Section: Discussioncontrasting

confidence: 46%

Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

Mančíková

Cruz

Inglada-Pérez

et al. 2015

Intl Journal of Cancer

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Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome-wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well-defined Southern European casecontrol collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR 5 1.64, p 5 1.0 3 10 222

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Section: Discussioncontrasting

confidence: 46%

Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

Mančíková

Cruz

Inglada-Pérez

et al. 2015

Intl Journal of Cancer

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“…This limitation is solved by genome-wide association studies (GWASs) in which the whole genome is analyzed without formulating any a priori hypothesis. GWASs on DTC allowed discovering novel variants, including those near FOXE1, DIRC3, NKX2-1 (15)(16)(17) and, more recently, those near IMMP2L, RARRES1, SNAPC4/CARD9, ARSB, BATF, DHX35, SPATA13, GALNTL4, and FOXA2 (18)(19)(20). However, to ensure a high quality and to prevent false-positive findings, highly stringent criteria are applied in the GWASs with the disadvantage of excluding SNPs truly associated with the risk.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Meta-analysis of Case–Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma

Figlioli

Elisei

Romei

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Linkage analyses and association studies suggested that inherited genetic variations play a role in the development of differentiated thyroid carcinoma (DTC).Methods: We combined the results from a genome-wide association study (GWAS) performed by our group and from published studies on DTC. With a first approach, we evaluated whether a SNP published as associated with the risk of DTC could replicate in our GWAS (using FDR as adjustment for multiple comparisons). With the second approach, meta-analyses were performed between literature and GWAS when both sources suggested an association, increasing the statistical power of the analysis.Results: rs1799814 (CYP1A1), rs1121980 (FTO), and 3 SNPs within 9q22 (rs965513, rs7048394, and rs894673)

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“…The advent of genome-wide association studies (GWAS) constituted a breakthrough in the ability to study the genetics of complex diseases. Single nucleotide polymorphisms (SNPs) associated with a low to medium risk for PTC have been described in several GWAS studies (5)(6)(7)(8)(9). The first variants uncovered by GWAS were rs965513 (9q22), rs944289 (14q13), rs116909374 (14q13), rs2439302 (8p12), and rs966423 (2q35) (5,6).…”

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Papillary Thyroid Carcinoma: Association Between Germline DNA Variant Markers and Clinical Parameters

Jendrzejewski

Liyanarachchi

Nagy

et al. 2016

Thyroid

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Background: Papillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients. Methods: In order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants (PTCSC3, MBIP, NKX2-1, FOXE1, DIRC3, PTCSC2, and NRG1) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score. Results: The risk allele of rs965513 was associated with larger tumor size ( p = 0.025) and extrathyroidal expansion (odd ratio [OR] = 1.29, p = 0.045). The variant rs2439302 showed association with lymph node metastasis (OR = 1.24, p = 0.016), and multifocality status of the tumor (OR = 1.24, p = 0.012). The expression of MBIP was associated with T stage ( p = 0.010). MBIP and PTCSC3 displayed lower expression in PTC tissue in males than in females ( p = 0.025 and p = 0.036, respectively). NKX2-1 displayed lower expression in patients with N1 stage ( p = 0.040). Conclusions: The studied germline risk alleles predisposing to PTC were associated with a more aggressive course of the disease reflected by larger tumor diameter, higher multifocality rate, and more advanced N stage at the time of diagnosis. These results show that germline variants not only predispose to PTC but also might impact its clinical course. However, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients.

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Novel Genome-Wide Association Study–Based Candidate Loci for Differentiated Thyroid Cancer Risk

Abstract: Our findings provide evidence for novel DTC susceptibility variants. Further studies are warranted to identify the specific genetic variants responsible for the observed associations and to functionally validate our in silico predictions.

Cited by 48 publications

References 32 publications

Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

A Comprehensive Meta-analysis of Case–Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma

Papillary Thyroid Carcinoma: Association Between Germline DNA Variant Markers and Clinical Parameters

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