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Association of benign thyroid diseases with thyroid cancer risk: a meta-analysis of prospective observational studies

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Abstract

Purpose

Evidence showed that benign thyroid disease was one of the risk factors for thyroid cancer. However, the results of some studies were inconsistent and were previously meta-analyses of case–control studies. Therefore, we performed a meta-analysis of prospective studies to investigate the relationship between benign thyroid diseases and thyroid cancer risk.

Methods

All eligible studies were identified via systematic searches of multiple literature databases. The combined RR (relative risk)/HR (hazard ratio) or SIR (standardized incidence ratio) with 95% confidence interval was calculated. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed.

Results

Twelve studies were eligible for inclusion in the meta-analysis. The pooled RR/HR of thyroid carcinoma in benign thyroid diseases was 4.39 (95% CI 3.22–5.55). The pooled SIR of thyroid carcinoma in benign thyroid diseases was 5.98 (95% CI 4.09–7.86). Subgroup analysis was performed using the type of benign thyroid diseases. Effect value was RR/HR: hyperthyroidism (RR/HR = 3.89, 95% CI = 1.69–6.08), hypothyroidism (RR/HR = 2.72, 95% CI = 1.04–4.41), and goiter (RR/HR = 22.18, 95% CI = 12.09–32.28). Effect value was SIR: hyperthyroidism (RR/HR = 5.96, 95% CI = 1.88–10.03), goiter (RR/HR = 7.65, 95% CI = 6.94–8.37), and thyroiditis (RR/HR = 3.25, 95% CI = 1.62–4.89).

Conclusions

Our study has shown that benign thyroid diseases might be associated with increased risk of thyroid cancer, especially in hyperthyroidism, hypothyroidism, and goiter. However, further investigation is needed to better understand the underlying biological mechanisms.

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Funding

This work was supported by National Natural Science Foundation of China (No. 81373071) and the Project for Anhui Province Academic Technology Leader Reserve Candidates’ Academic Research Activities (2017H108).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China

    L. Liang, M.-J. Hu, Q. Zhang & F. Huang

  2. Department of Head and Neck, Breast Surgery, Anhui Provincial Cancer Hospital (West Branch of The First Affiliated Hospital of University of Science and Technology of China), No. 107 East Huanhu Road, Shushan Districts, Hefei, 230088, Anhui, China

    X.-C. Zheng & S.-Y. Wang

  3. Central Laboratory of Preventive Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China

    F. Huang

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  1. L. Liang
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Contributions

LL acquisition of data, analysis and interpretation of data, drafted the manuscript; MH completed the database searches and selected, reviewed the articles and extracted the data; XZ and QZ collection and assembly of data, and performed the data analyses; SW and FH conception and design of the study, discussed the idea of the meta-analysis, critical revision of the article for important intellectual content, submitted the paper. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to S.-Y. Wang or F. Huang.

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Conflict of interest

The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Since this is a meta-analysis, informed consent is not applicable.

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40618_2018_968_MOESM1_ESM.eps

Supplementary material 1 Forest plot for subgroup analysis based on the NOS quality score. Error bars indicate 95% CI. Solid diamonds represent each record in the meta-analysis. Hollow diamonds represent pooled RR/HR (EPS 58132 kb)

40618_2018_968_MOESM2_ESM.eps

Supplementary material 2 Forest plot for subgroup analysis based on whether adjusted for multivariate. Error bars indicate 95% CI. Solid diamonds represent each record in the meta-analysis. Hollow diamonds represent pooled RR/HR (EPS 75312 kb)

Supplementary material 3 Funnel plot with effect value of SIR (EPS 63129 kb)

Supplementary material 4 Funnel plot with effect value of RR/HR after trim and fill method (EPS 36320 kb)

40618_2018_968_MOESM5_ESM.eps

Supplementary material 5 Sensitivity analysis plot: investigated the influence of a single record on the overall SIR estimate by removing each record in each turn (EPS 38201 kb)

Supplementary material 6 Characteristics of studies included in the meta-analysis (DOC 274 kb)

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Liang, L., Zheng, XC., Hu, MJ. et al. Association of benign thyroid diseases with thyroid cancer risk: a meta-analysis of prospective observational studies. J Endocrinol Invest 42, 673–685 (2019). https://doi.org/10.1007/s40618-018-0968-z

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