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Vol 70, No 5 (2019)
Review Article
Published online: 2019-10-25
Submitted: 2019-02-22
Accepted: 2019-04-04
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Clinical implications of GWAS variants associated with differentiated thyroid cancer

Jarosław P. Jendrzejewski, Krzysztof Sworczak, Daniel F. Comiskey, Albert de la Chapelle
DOI: 10.5603/EP.a2019.0027
·
Pubmed: 31681970
·
Endokrynologia Polska 2019;70(5):423-429.

open access

Vol 70, No 5 (2019)
Review Article
Published online: 2019-10-25
Submitted: 2019-02-22
Accepted: 2019-04-04

Abstract

The genetic risk of differentiated thyroid cancer (DTC) probably consists of multiple low-penetrance, single-nucleotide polymorphisms (SNP). Such markers are difficult to uncover by linkage analysis but can be revealed by association studies. Genome-wide association studies (GWASs) have uncovered 31 SNPs associated with DTC. These markers carry a low to moderate risk for DTC, but their cumulative effect increases with each successive risk allele. These data support the important contribution of low penetrance variants in the pathogenesis of DTC. Contrary to somatic mutations such as BRAFV600E, germline variants can be ascertained prior to surgical treatment. Therefore, we hypothesise that GWAS SNPs might impact the clinical course of DTC and we can benefit from this knowledge in choosing a treatment strategy. Several associations between clinical factors and GWAS markers have been reported so far. The most important are associations between rs966423 and mortality (HR = 1.60, p = 0.038), extrathyroidal extension (ETE) (OR = 1.57, p = 0.019); rs965513 and tumour diameter (slope of regression 0.14, p = 0.025), lymph node metastasis (OR = 1.59, p = 0.030) and ETE (OR = 1.29, p = 0.045); rs944289 and distant metastasis (OR = 0.58, p = 0.042); and rs116909374 and lymph node metastasis (OR = 0.61, p = 0.016). These findings show that GWAS SNPs are not only the ignition factors (together with environmental factors) for malignant transformation of thyrocytes but might also impact the clinical course of DTC. Surprisingly, it is not always the risk allele for DTC that is associated with worse clinical outcome. The second interesting observation is that GWAS SNPs show different associations with DTC clinical features depending on their histological subtypes. These point to the complexity of DTC with putatively different roles of genes at different stages of DTC development. (Endokrynol Pol 2019; 70 (5): 423–429)

Abstract

The genetic risk of differentiated thyroid cancer (DTC) probably consists of multiple low-penetrance, single-nucleotide polymorphisms (SNP). Such markers are difficult to uncover by linkage analysis but can be revealed by association studies. Genome-wide association studies (GWASs) have uncovered 31 SNPs associated with DTC. These markers carry a low to moderate risk for DTC, but their cumulative effect increases with each successive risk allele. These data support the important contribution of low penetrance variants in the pathogenesis of DTC. Contrary to somatic mutations such as BRAFV600E, germline variants can be ascertained prior to surgical treatment. Therefore, we hypothesise that GWAS SNPs might impact the clinical course of DTC and we can benefit from this knowledge in choosing a treatment strategy. Several associations between clinical factors and GWAS markers have been reported so far. The most important are associations between rs966423 and mortality (HR = 1.60, p = 0.038), extrathyroidal extension (ETE) (OR = 1.57, p = 0.019); rs965513 and tumour diameter (slope of regression 0.14, p = 0.025), lymph node metastasis (OR = 1.59, p = 0.030) and ETE (OR = 1.29, p = 0.045); rs944289 and distant metastasis (OR = 0.58, p = 0.042); and rs116909374 and lymph node metastasis (OR = 0.61, p = 0.016). These findings show that GWAS SNPs are not only the ignition factors (together with environmental factors) for malignant transformation of thyrocytes but might also impact the clinical course of DTC. Surprisingly, it is not always the risk allele for DTC that is associated with worse clinical outcome. The second interesting observation is that GWAS SNPs show different associations with DTC clinical features depending on their histological subtypes. These point to the complexity of DTC with putatively different roles of genes at different stages of DTC development. (Endokrynol Pol 2019; 70 (5): 423–429)

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Keywords

genome-wide association studies; GWAS; papillary thyroid carcinoma; PTC; genetic predisposition

About this article
Title

Clinical implications of GWAS variants associated with differentiated thyroid cancer

Journal

Endokrynologia Polska

Issue

Vol 70, No 5 (2019)

Pages

423-429

Published online

2019-10-25

DOI

10.5603/EP.a2019.0027

Pubmed

31681970

Bibliographic record

Endokrynologia Polska 2019;70(5):423-429.

Keywords

genome-wide association studies
GWAS
papillary thyroid carcinoma
PTC
genetic predisposition

Authors

Jarosław P. Jendrzejewski
Krzysztof Sworczak
Daniel F. Comiskey
Albert de la Chapelle

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