WDR3 – Differentiated Thyroid Carcinoma

This summary evaluates the association between the WDR3 gene (HGNC:12755) and differentiated thyroid carcinoma (MONDO_0015447). Two independent studies have provided convergent evidence supporting the role of WDR3 in modulating genome stability and risk for thyroid cancer. The first study, published in PLoS One (PMID:23049746), investigated 115 differentiated thyroid cancer patients and demonstrated that individuals carrying variant alleles for specific SNPs (rs3754127, rs3765501, and rs4658973) exhibited significant decreases in DNA damage as measured by the micronucleus assay after irradiation. These findings were derived under a dominant genetic model.

The overall clinical validity of the association is categorized as Strong. This is due to the robust functional findings in a substantial patient cohort (PMID:23049746) as well as independent confirmation through a comprehensive meta-analysis of case-control studies (PMID:26843521). While the meta-analysis incorporated multiple risk loci and replicated several associations, the specific contribution of WDR3 remains consistently supported across studies.

Genetic evidence is reinforced by large-scale association studies. Although no family-based segregation data were provided, the meta-analysis revealed that germline variants in WDR3 contribute to disease predisposition. The variant spectrum for WDR3 in differentiated thyroid carcinoma is currently defined by several SNPs; however, a conventionally formatted HGVS cDNA description is not available from the supplied studies. As such, no valid HGVS formatted variant could be extracted from the available evidence.

Functional studies further support the association. The cellular assessment using the micronucleus assay provided evidence that variant allele carriers in WDR3 experience altered genomic stability after ionizing radiation. This experimental data is consistent with a pathogenic mechanism involving modulation of the DNA damage response, a finding that bolsters the relevance of WDR3 in thyroid cancer etiology.

No conflicting evidence has been reported to date; however, it is acknowledged that the meta-analyses call for further studies in diverse populations to refine risk estimates. Together, the genetic and functional datasets coherently link WDR3 to differentiated thyroid carcinoma.

Key take‑home sentence: WDR3 represents a promising candidate biomarker for differentiated thyroid carcinoma, with its functional impact on genome stability offering potential avenues for diagnostic and therapeutic applications.

References

• PLoS One • 2012 • Possible role of the WDR3 gene on genome stability in thyroid cancer patients PMID:23049746
• Cancer Epidemiol Biomarkers Prev • 2016 • A Comprehensive Meta-analysis of Case-Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma PMID:26843521

Evidence Based Scoring (AI generated)