Thyroid dysfunction and cancer incidence: a systematic review and meta-analysis

in Endocrine-Related Cancer
Authors:
Thi-Van-Trinh Tran Cancer and Radiation Group, Center for Research in Epidemiology and Population Health, INSERM U1018, Paris Sud-Paris Saclay University, Gustave Roussy, Villejuif, France

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Cari M Kitahara Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Florent de Vathaire Cancer and Radiation Group, Center for Research in Epidemiology and Population Health, INSERM U1018, Paris Sud-Paris Saclay University, Gustave Roussy, Villejuif, France

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Marie-Christine Boutron-Ruault Health Across Generations Group, Center for Research in Epidemiology and Population Health, INSERM U1018, Paris Sud-Paris Saclay University, Gustave Roussy, Villejuif, France

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Neige Journy Cancer and Radiation Group, Center for Research in Epidemiology and Population Health, INSERM U1018, Paris Sud-Paris Saclay University, Gustave Roussy, Villejuif, France

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Correspondence should be addressed to T-V-T Tran: Thivantrinh.TRAN@gustaveroussy.fr
DOI:
https://doi.org/10.1530/ERC-19-0417
Volume/Issue:
Volume 27: Issue 4
Article Type:
Research Article
Page Range:
245–259
Online Publication Date:
Apr 2020
Copyright:
© 2020 Society for Endocrinology 2020
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In this study, we aimed to evaluate site-specific cancer risks associated with hyperthyroidism or hypothyroidism. We performed a systematic review of observational studies reporting associations between hyperthyroidism or hypothyroidism and subsequent site-specific cancer incidence, in MEDLINE and the COCHRANE library (inception-28/01/2019) (PROSPERO: CRD42019125094). We excluded studies with thyroid dysfunction evaluated as a cancer biomarker or after prior cancer diagnosis and those considering transient thyroid dysfunction during pregnancy or severe illnesses. Risk of bias was assessed using a modified Newcastle–Ottawa scale. Risk estimates were pooled using random-effects models when ≥5 studies reported data for a specific cancer site. Twenty studies were included, of which 15 contributed to the meta-analysis. Compared to euthyroidism, hyperthyroidism was associated with higher risks of thyroid (pooled risk ratio: 4.49, 95%CI: 2.84–7.12), breast (pooled risk ratio: 1.20, 95%CI: 1.04–1.38), and prostate (pooled risk ratio: 1.35, 95%CI: 1.05–1.74), but not respiratory tract (pooled risk ratio: 1.06, 95%CI: 0.80–1.42) cancers. Hypothyroidism was associated with a higher risk of thyroid cancer within the first 10 years of follow-up only (pooled risk ratio: 3.31, 95%CI: 1.20–9.13). There was no or limited evidence of thyroid dysfunction-related risks of other cancer sites. In conclusion, thyroid dysfunction was associated with increased risks of thyroid, breast, and prostate cancers. However, it remains unclear whether these findings represent causal relationships because information on treatments and potential confounders was frequently lacking.

Supplementary Materials

    • Appendix 1. PRISMA checklist (page numbers refer to the submitted manuscript)
    • Appendix 2. Search terms used in the systematic review
    • Appendix 3. Modified Newcastle-Ottawa for risk of bias assessment
    • Appendix 4. Overall risk of bias of 20 included studies
    • Appendix 5. Thyroid dysfunction categorization based on thyroid hormone levels
    • Appendix 6. Studies on the association between thyroid dysfunction and cancer mortality
    • Supplementary Figure 1. Funnel plot for publication bias of the meta-analysis studying the association of hyperthyroidism and thyroid cancer risk. Egger test (p=0.65) revealed no evidence of publication bias
    • Supplementary Figure 2. Funnel plot for publication bias of the meta-analysis studying the association of hyperthyroidism and breast cancer risk. Egger test (p=0.85) revealed no evidence of publication bias
    • Supplementary Figure 3. Funnel plot for publication bias of the meta-analysis studying the association of hyperthyroidism and prostate cancer risk. Egger test (p=0.41) revealed no evidence of publication bias
    • Supplementary Figure 4. Funnel plot for publication bias of the meta-analysis studying the association of hyperthyroidism and the risk of respiratory tract cancer. Egger test (p=0.49) revealed no evidence of publication bias
    • Supplementary Figure 5. Funnel plot for publication bias of the meta-analysis studying the association of hypothyroidism and thyroid cancer risk. Egger test (p=0.53) revealed no evidence of publication bias
    • Supplementary Figure 6. Funnel plot for publication bias of the meta-analysis studying the association of hypothyroidism and breast cancer risk. Egger test (p=0.66) revealed no evidence of publication bias
    • Supplementary Figure 7. Subgroup analysis by sex of the association between thyroid dysfunction and thyroid cancer risk. The test found no substantial difference between men and women. A. For hyperthyroidism analysis (p=0.43), B. For hypothyroidism analysis (p=0.10). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. TC: Thyroid cancer, nr: Not reported, PY: person-year.
    • Supplementary Figure 8. Subgroup analysis by treatment methods of the association between hyperthyroidism and thyroid cancer risk. The test found no substantial difference among different treatment methods (p=0.22). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. TC: Thyroid cancer, PY: person-year, RAI: Radioactive iodine.
    • Supplementary Figure 9. Subgroup analysis by treatment methods of the association between hyperthyroidism and breast cancer risk. The test found no substantial difference among different treatment methods (p=0.54). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. BC: Breast cancer, nr: Not reported, PY: person-year, RAI: Radioactive iodine.
    • Supplementary Figure 10. Subgroup analysis by treatment methods of the association between hyperthyroidism and prostate cancer risk. The test found no substantial difference among different treatment methods (p=0.27). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. PC: Prostate cancer, nr: Not reported, RAI: Radioactive iodine.
    • Supplementary Figure 11. Subgroup analysis by treatment methods of the association between hyperthyroidism and respiratory tract cancer risk. The test found no substantial difference among different treatment methods (p=0.47). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. RTC: Respiratory tract cancer, nr: Not reported, RAI: Radioactive iodine.
    • Supplementary Figure 12. Subgroup analysis by treatment methods of the association between hypothyroidism and breast cancer risk. The test found a statistically significant difference among different treatment methods (p=0.03). Overall risk ratios are displayed as diamonds. The size of each square is proportional to the weight of the study. BC: Breast cancer, THRT: Thyroid hormone replacement therapy.
    • Supplementary Figure 13. Influence analysis of the association between hyperthyroidism and thyroid cancer risk
    • Supplementary Figure 14. Influence analysis of the association between hyperthyroidism and breast cancer risk
    • Supplementary Figure 15. Influence analysis of the association between hyperthyroidism and prostate cancer risk
    • Supplementary Figure 16. Influence analysis of the association between hyperthyroidism and respiratory tract cancer risk
    • Supplementary Figure 17. Influence analysis of the association between hypothyroidism and thyroid cancer risk
    • Supplementary Figure 18. Influence analysis of the association between hypothyroidism and breast cancer risk
    • Supplementary Table 1. Association between hyperthyroidism and the risk of different cancer sites other than thyroid, breast, prostate and respiratory tract cancer. Metso 2007: Results estimated based on a figure reported primary results of the article, exact results were not available.
    • Supplementary Table 2. Association between hypothyroidism and the risk of different cancer sites other than thyroid and breast cancer
    • Supplementary Table 3. Subgroup and sensitivity analysis of the association between thyroid dysfunction and thyroid cancer risk
    • Supplementary Table 4. Subgroup and sensitivity analysis of the association between thyroid dysfunction and breast cancer risk
    • Supplementary Table 5. Subgroup and sensitivity analysis of the association between hyperthyroidism and prostate cancer risk
    • Supplementary Table 6. Subgroup and sensitivity analysis of the association between hyperthyroidism and the risk of respiratory tract cancer

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
15
Received Date:
04 Feb 2020
Accepted Date:
07 Feb 2020
Print Publication Date:
01 Apr 2020
Online Publication Date:
Apr 2020
Keywords:
hyperthyroidism; hypothyroidism; cancer; incidence; epidemiological studies; meta-analysis

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