Clinical implications of GWAS variants associated with differentiated thyroid cancer.

Clinical implications of GWAS variants associated with differentiated thyroid cancer. Endokrynol Pol. 2019;70(5):423-429 Authors: Jendrzejewski JP, Sworczak K, Comiskey DF, de la Chapelle A 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); ...
Source: Endokrynologia Polska - Category: Endocrinology Authors: Tags: Endokrynol Pol Source Type: research