Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Oct 30;22(21):11794.
doi: 10.3390/ijms222111794.

Modifier Role of Common RET Variants in Sporadic Medullary Thyroid Carcinoma

Anna Skalniak  1 , Małgorzata Trofimiuk-Müldner  1 , Elwira Przybylik-Mazurek  1 , Alicja Hubalewska-Dydejczyk  1
Affiliations
Clinical Trial

Modifier Role of Common RET Variants in Sporadic Medullary Thyroid Carcinoma

Anna Skalniak et al. Int J Mol Sci. .

Abstract

Background: Although the disease-causing effect of pathogenic variants in the gene RET has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exons 10, 11, and 13-16 that are commonly detected during routine diagnostic testing might have any modifying effect on MTC. Methods: In sporadic MTC patients with no pathogenic variants but with or without common variants in RET, the following variants were evaluated: rs1799939 (p.G691S), rs1800861 (p.L769=), rs1800862 (p.S836=), rs2472737 in intron 14, and rs1800863 (p.S904=). Results: After Bonferroni correction, none of the variants were statistically significantly associated with disease outcome when analysed independently. The MTC group was divided into three genetically different clusters by unsupervised k-means clustering. Those clusters differed significantly in the age at diagnosis. A trend towards the association of given clusters with metabolic disorders and with remission state was identified. Conclusions: Although common variants in RET are not responsible for the risk of MTC, their analysis might turn out useful in the prediction of a patient's clinical outcome. Importantly, this analysis would come with no additional cost in laboratories with a diagnostic procedure based on exon sequencing.

Keywords: RET variants; medullary thyroid carcinoma; modifier.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphic representation of clusters discriminated by unsupervised k−means clusterisation.
Figure 2
Figure 2
Graphic representation of age distributions in the obtained clusters.
Figure 3
Figure 3
Correspondence analysis plot−relationship between clusters and remission state.
See this image and copyright information in PMC

References

    1. Wells S.A., Asa S.L., Dralle H., Elisei R., Evans D.B., Gagel R.F., Lee N., Machens A., Moley J.F., Pacini F., et al. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid. 2015;25:567–610. doi: 10.1089/thy.2014.0335. - DOI - PMC - PubMed
    1. Machens A., Frank-Raue K., Lorenz K., Rondot S., Raue F., Dralle H. Clinical Relevance of RET Variants G691S, L769L, S836S and S904S to Sporadic Medullary Thyroid Cancer. Clin. Endocrinol. 2012;76:691–697. doi: 10.1111/j.1365-2265.2011.04293.x. - DOI - PubMed
    1. Baumgartner-Parzer S.M., Lang R., Wagner L., Heinze G., Niederle B., Kaserer K., Waldhäusl W., Vierhapper H. Polymorphisms in Exon 13 and Intron 14 of the RET Protooncogene: Genetic Modifiers of Medullary Thyroid Carcinoma? J. Clin. Endocrinol. Metab. 2005;90:6232–6236. doi: 10.1210/jc.2005-1278. - DOI - PubMed
    1. Fugazzola L., Muzza M., Mian C., Cordella D., Barollo S., Alberti L., Cirello V., Dazzi D., Girelli M.E., Opocher G., et al. RET Genotypes in Sporadic Medullary Thyroid Cancer: Studies in a Large Italian Series. Clin. Endocrinol. 2008;69:418–425. doi: 10.1111/j.1365-2265.2008.03218.x. - DOI - PubMed
    1. Weinhaeusel A., Scheuba C., Lauss M., Kriegner A., Kaserer K., Vierlinger K., Haas O.A., Niederle B. The Influence of Gender, Age, and RET Polymorphisms on C-Cell Hyperplasia and Medullary Thyroid Carcinoma. Thyroid. 2008;18:1269–1276. doi: 10.1089/thy.2008.0139. - DOI - PubMed

Publication types

Substances

Supplementary concepts