A combined genetic and bioinformatic analysis implicates the CDKN1A rs1059234 variant in differentiated thyroid carcinoma susceptibility.

Abstract

Objective: To evaluate the association of CDKN1A (rs1801270 and rs1059234) and CDKN1B (rs2066827 and rs34330) polymorphisms with differentiated thyroid carcinoma (DTC) risk and to explore potential functional impacts through in silico analyses.

Subjects and methods: This case-control study included 185 DTC patients and 236 healthy controls. Genotyping was performed using TaqMan® assays, and associations with DTC risk and clinicopathological features were assessed via logistic regression. Bioinformatic tools were used to predict the structural and regulatory effects of the studied polymorphisms.

Results: The CDKN1A rs1059234 polymorphism showed a statistically significant association with increased DTC risk, particularly for the CT genotype (odds ratio = 6.575; 95% confidence interval: 4.004-10.803; p < 0.0001). In silico analyses suggested that rs1059234 may modify microRNA binding sites within the 3'UTR, potentially modifying the post-transcriptional regulation of CDKN1A. This variant was not correlated with tumor characteristics, including tumor size, histological subtype, or meta-static status. No significant associations were found for rs1801270, rs2066827, or rs34330. Predictions for missense variants (rs1801270 and rs2066827) were inconsistent, with some tools indicating possible destabilizing effects on p21 or p27 protein structure.

Conclusion: The CDKN1A rs1059234 polymorphism may represent a candidate susceptibility marker for DTC, possibly through altered post-transcriptional regulation of p21. However, due to the moderate sample size and the absence of functional validation, these findings should be considered hypothesis-generating and require independent replication in larger cohorts with experimental validation. The remaining investigated variants did not meaningfully influence DTC risk in this study.