Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis

Abstract

Background and AimsThe extent of surgical treatment for most patients with thyroid cancer (TC) remains controversial and varies widely. As an emerging technology, genetic testing facilitates tumor typing and disease progression monitoring and is expected to influence the choice of surgical approach for patients with TC. Recent genome-wide association studies (GWASs) have identified that rs2439302 (8p12) variants near NRG1 are associated with TC risk; however, the results remain inconclusive. Therefore, we aimed to perform a meta-analysis to clarify the association between rs2439302 variants and the risk of TC.MethodsWe search eligible studies using Pubmed, Scopus, Embase, Web of Science, and Cochrane library by July 2021. We analyzed the pooled OR and the corresponding 95% confidence interval (95% CI) of the included studies and then conducted subgroup analysis according to the ethnicity. We also performed a sensitivity analysis to validate the findings.ResultsThis meta-analysis finally included 7 studies involving 6,090 cases and 14,461 controls. Results showed that the G allele of the rs2439302 polymorphism was a significant risk factor of TC in Allele (G/C), Dominant (GG+GC/CC), Recessive (GG/GC+CC), Homozygote (GG/CC), Heterozygote (GC/CC) models, with pooled ORs of 1.38 (95%CI, 1.31–1.45), 1.51 (95%CI, 1.41–1.62), 1.52 (95%CI, 1.40–1.66), 1.90 (95%CI, 1.71–2.10), and 1.40 (95%CI, 1.30–1.51), respectively. The subgroup analysis showed that rs2439302 polymorphism was associated with higher TC risk in different ethnicities with OR > 1. The sensitivity analysis exhibited that the results were stable by omitting any included studies.ConclusionsThe study revealed that rs2439302 variants were associated with higher TC risk and may have a major influence on the choice of operative approach for patients with TC.

The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update

“…Several studies demonstrated an association between NRG1 rs2439302 and PTC [ 62 , 63 , 64 ]. Moreover, a recent meta-analysis consolidated the previous results stating that the SNP rs2439302 variants of the gene encoding NRG1 carry a high thyroid cancer risk, especially in Chinese populations compared to Japanese populations or populations from the United States of America [ 65 ].…”

The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease

“…In this study, we tried to clarify the underlying molecular mechanism. SNP rs2439302 was within the first intron of NRG1 on 8p12, which was first described to be significantly correlated with thyroid cancer (Guo et al, 2022). Thyroid hormones are important regulators of neurodevelopment early in life (Leung and Leung, 2019;Salerno et al, 2020).…”

Drug repositioning in thyroid cancer: from point mutations to gene fusions

“…Besides the variants reported in the above-mentioned genes, there are also polymorphisms associated with TC ( 58 ). For instance, neuregulin 1 ( NRG1 ) acts as an oncogene through its role as a glycoprotein that mediates cell-to-cell signaling ( 59 ).…”