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

Abstract

Background and aims: The 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.

Methods: We 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.

Results: This 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.

Conclusions: The 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.

Keywords: genome-wide association studies; meta-analysis; rs2439302; single nucleotide polymorphism; thyroid cancer.

Figure 1

The flow gram of the study was shown.

Figure 2

Forest plots for the meta-analysis of rs2439302 polymorphism and the risk of TC. (A) G vs. C (allele model). (B) GG plus CG vs. CC (dominant model). (C) GG vs. CC plus CG (recessive model). (D) GG vs. CC (homozygous model). (E) GC vs. CC (heterozygous model). OR, odds ratios; CI, confidence interval.

Figure 3

Forest plots for the subgroup-analysis of rs9929218 polymorphism and the risk of thyroid cancer based on ethnicity. (A) G vs. C (allele model). (B) GG plus CG vs. CC (dominant model). (C) GG vs. CC plus CG (recessive model). (D) GG vs. CC (homozygous model). (E) GC vs. CC (heterozygous model). OR, odds ratios; CI, confidence interval.

Figure 4

Publication bias analysis for rs2439302 polymorphism and the TC risk for G vs. C (allele model). (A) A funnel plot of publication bias analysis was performed to explore the correlation between rs2439302 polymorphism and TC risk. The methods based on linear regression proposed by (B) Begg plot and (C) Egger test were used to evaluate the asymmetry of the funnel plot. (D) The method based on linear regression proposed by the Egger test based on arcsine difference was utilized to analyze the asymmetry of the funnel plot.