Zinc Status and Occurrence of Thyroid Cancer: Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Inclusion Criteria
2.3. Exclusion Criteria
2.4. Study Selection Process
2.5. Data Extraction
2.6. Risk of Bias and Quality Assessment
2.7. Data Synthesis
3. Results
3.1. Survey and Selection of Studies
3.2. Characteristics of the Studies
3.3. Meta-Analysis of the Studies
3.4. Risk of Bias Analysis
4. Discussion
Important Deviations from the Published Protocol
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Boufraqech, M.; Patel, D.; Xiong, Y.; Kebebew, E. Diagnosis of thyroid cancer: State of the art. Expert Opin. Med. Diagn. 2013, 7, 331–342. [Google Scholar] [CrossRef] [PubMed]
- Rahib, L.; Smith, B.D.; Aizenberg, R.; Rosenzweig, A.B.; Fleshman, J.M.; Matrisian, L.M. Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Res. 2014, 74, 2913–2921. [Google Scholar] [CrossRef] [PubMed]
- Chen, D.W.; Lang, B.H.H.; McLeod, D.S.A.; Newbold, K. Haymart, MR Thyroid cancer. Lancet 2023, 401, 1531–1544. [Google Scholar] [CrossRef]
- Boucai, L.; Zafereo, M. Cabanillas, ME Thyroid Cancer: A Review. JAMA 2024, 331, 425–435. [Google Scholar] [CrossRef]
- Ron, E.; Lubin, J.H.; Shore, R.E.; Mabuchi, K.; Modan, B.; Pottern, L.M.; Schneider, A.B.; Tucker, M.A.; Boice, J.D., Jr. Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies. Radiat. Res. 1995, 141, 259–277. [Google Scholar] [CrossRef]
- Morton, L.M.; Karyadi, D.M.; Stewart, C.; Bogdanova, T.I.; Dawson, E.T.; Steinberg, M.K.; Dai, J.; Hartley, S.W.; Schonfeld, S.J.; Sampson, J.N.; et al. Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident. Science 2021, 372, 2538. [Google Scholar] [CrossRef]
- Nettore, I.C.; Colao, A. Macchia PENutritional Environmental Factors in Thyroid Carcinogenesis. Int. J. Environ. Res. Public Health 2018, 15, 1735. [Google Scholar] [CrossRef]
- Cho, Y.A.; Kim, J. Thyroid cancer risk and smoking status: A meta-analysis. Cancer Causes Control. 2014, 25, 1187–1195. [Google Scholar] [CrossRef]
- Pappa, T.; Alevizaki, M. Obesity and thyroid cancer: A clinical update. Thyroid 2014, 24, 190–199. [Google Scholar] [CrossRef]
- Sangsefidi, Z.S.; Ghafouri-Taleghani, F.; Zakavi, S.R.; Norouzy, A.; Kashanifar, R.; Pourbaferani, R.; Safarian, M.; Hosseinzadeh, M. Major dietary patterns and differentiated thyroid cancer. Clin. Nutr. ESPEN 2019, 33, 195–201. [Google Scholar] [CrossRef] [PubMed]
- Neto, V.; Leitão, C.; Estrela, M.; Fardilha, M.; Herdeiro, M.T.; Nunes, A. The influence of nutrition in nodular thyroid pathology: A systematic review. Crit. Rev. Food Sci. Nutr. 2024, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Ma, Q.; Li, Y.; Yu, G.; Liu, S.; Jiang, Y.; Duan, H.; Wang, D.; He, Y.; Chen, X.; Yao, N.; et al. Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: A Cross-sectional Study. Biol. Trace Elem. Res. 2024, 202, 4357–4366. [Google Scholar] [CrossRef]
- Stojsavljević, A.; Rovčanin, B.; Jagodić, J.; Krstić, Đ.; Paunović, I.; Gavrović-Jankulović, M.; Manojlović, D. Alteration of Trace Elements in Multinodular Goiter, Thyroid Adenoma, and Thyroid Cancer. Biol. Trace Elem. Res. 2021, 199, 4055–4065. [Google Scholar] [CrossRef] [PubMed]
- Kazi Tani, L.S.; Gourlan, A.T.; Dennouni-Medjati, N.; Telouk, P.; Dali-Sahi, M.; Harek, Y.; Sun, Q.; Hackler, J.; Belhadj, M.; Schomburg, L.; et al. Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer. Front. Med. 2021, 8, 698167. [Google Scholar] [CrossRef]
- Mehl, S.; Sun, Q.; Görlich, C.L.; Hackler, J.; Kopp, J.F.; Renko, K.; Mittag, J.; Schwerdtle, T.; Schomburg, L. Cross-sectional analysis of trace element status in thyroid disease. J. Trace Elem. Med. Biol. 2020, 58, 126430. [Google Scholar] [CrossRef] [PubMed]
- Bibi, K.; Shah, M.H. Appraisal of Metal Imbalances in the Blood of Thyroid Cancer Patients in Comparison with Healthy Subjects. Biol. Trace Elem. Res. 2020, 198, 410–422. [Google Scholar] [CrossRef] [PubMed]
- Baltaci, A.K.; Dundar, T.K.; Aksoy, F.; Mogulkoc, R. Changes in the Serum Levels of Trace Elements Before and After the Operation in Thyroid Cancer Patients. Biol. Trace Elem. Res. 2017, 175, 57–64. [Google Scholar] [CrossRef] [PubMed]
- Al-Sayer, H.; Mathew, T.C.; Asfar, S.; Khourshed, M.; Al-Bader, A.; Behbehani, A.; Dashti, H. Serum changes in trace elements during thyroid cancers. Mol. Cell. Biochem. 2004, 260, 1–5. [Google Scholar] [CrossRef]
- Maywald, M.; Wessels, I.; Rink, L. Zinc Signals and Immunity. Int. J. Mol. Sci. 2017, 18, 2222. [Google Scholar] [CrossRef]
- King, J.C.; Brown, K.H.; Gibson, R.S.; Krebs, N.F.; Lowe, N.M.; Siekmann, J.H.; Raiten, D.J. Biomarkers of Nutrition for Development (BOND)-Zinc, Review. J. Nutr. 2015, 146, 858S–885S. [Google Scholar] [CrossRef] [PubMed]
- Fung, E.B.; Ritchie, L.D.; Woodhouse, L.R.; Roehl, R.; King, J. CZinc absorption in women during pregnancy lactation: Alongitudinal study. Am. J. Clin. Nutr. 1997, 66, 80–88. [Google Scholar] [CrossRef]
- Wessells, K.R.; Brown, K.H. Estimating the global prevalence of zinc deficiency: Results based on zinc availability in national food supplies and the prevalence of stunting. PLoS ONE 2012, 7, 50568. [Google Scholar] [CrossRef]
- Severo, J.S.; Morais, J.B.S.; Freitas, T.E.C.; Andrade, A.L.P.; Feitosa, M.M.; Fontenelle, L.C.; de Oliveira, A.R.S.; Cruz, K.J.C.; Marreiro, D. The Role of Zinc in Thyroid Hormones Metabolism. Int. J. Vitam. Nutr. Res. 2019, 89, 80–88. [Google Scholar] [CrossRef]
- Yao, G.; Wang, Z.; Xie, R.; Zhanghuang, C.; Yan, B. Trace element zinc metabolism and its relation to tumors. Front. Endocrinol. 2024, 15, 1457943. [Google Scholar] [CrossRef]
- Nguyen, L.T.D.; Gunathilake, M.; Lee, J.; Kim, J. Association between dietary habits and incident thyroid cancer: A prospective cohort study. Front. Nutr. 2023, 10, 1104925. [Google Scholar] [CrossRef]
- Rezaei, M.; Javadmoosavi, S.Y.; Mansouri, B.; Azadi, N.A.; Mehrpour, O.; Nakhaee, S. Thyroid dysfunction: How concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer. Environ. Sci. Pollut. Res. Int. 2019, 26, 35787–35796. [Google Scholar] [CrossRef] [PubMed]
- Stroup, D.F.; Berlin, J.A.; Morton, S.C.; Olkin, I.; Williamson, G.D.; Rennie, D.; Moher, D.; Becker, B.J.; Sipe, T.A.; Thacker, S.B. Meta-analysis of observational studies in epidemiology: Aproposal for reporting Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000, 283, 2008–2012. [Google Scholar] [CrossRef] [PubMed]
- Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ 2009, 6, e1000100. [Google Scholar] [CrossRef] [PubMed]
- Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef]
- Higgins, J.P.T.; Thomas, J.; Chandler, J.; Cumpston, M.; Li, T.; Page, M.J.; Welch, V.A. (Eds.) Cochrane Handbook for Systematic Reviews of Interventions [Online], 2nd ed.; Cochrane Collaboration: Oxford, UK, 2019; Available online: https://training.cochrane.org/handbook (accessed on 19 December 2023).
- Wells, G.A.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses [Online]; Ottawa Hospital Research Institute: Ottawa, ON, USA, 2000; Available online: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 6 November 2023).
- Przybylik-Mazurek, E.; Zagrodzki, P.; Kuźniarz-Rymarz, S.; Hubalewska-Dydejczyk, A. Thyroid disorders-assessments of trace elements, clinical, and laboratory parameters. Biol. Trace Elem. Res. 2011, 141, 65–75. [Google Scholar] [CrossRef]
- Emami, A.; Nazem, M.R.; Shekarriz, R.; Hedayati, M. Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary thyroid carcinoma: A cross-sectional study. Nutrition 2017, 41, 86–89. [Google Scholar] [CrossRef]
- Chung, H.K.; Nam, J.S.; Ah, C.W.; Lee, Y.S.; Kim, K.R. Some Elements in Thyroid Tissue are Associated with More Advanced Stage of Thyroid Cancer in Korean Women. Biol. Trace Elem. Res. 2016, 171, 54–62. [Google Scholar] [CrossRef] [PubMed]
- Ma, Q.; Li, Y.; Yu, G.; Liu, S.; Jiang, Y.; Duan, H.; Wang, D.; He, Y.; Yao, N.; Wan, H.; et al. Single and combined associations of serum metal with thyroid nodules: A cross-sectional study. Rev. Cuba. Med. 2023, 33 (Suppl. S1), A80–A81. [Google Scholar]
- Farrokhi Yekta, R.; Arefi Oskouie, A.; Taheri, S.; Daneshyar, H. The evaluation of serum micro and trace elements in patients with papillary thyroid carcinoma and multinodular goiter. Trace Elem. Electrolytes 2019, 36, 215–221. [Google Scholar] [CrossRef]
- Nasiroglu Imga, N.; Berker, D.; Baba, S.; Kücükler, K.; Navdar Başaran, M.; Dağlar, G.; Guler, S. The role of serum zinc and copper levels in predicting malignancy in differentiated thyroid cancers. Trace Elem. Electrolytes 2017, 34, 111–117. [Google Scholar] [CrossRef]
- Azcano, G.A.; Susana, M.; Luís Manuel, F.; Vladimir, G.Y. Analysis multivariate laboratory data en he diagnosis of neoplasms malignant: VII. Rev. Cuba. Med. 1985, 24, 580–591. [Google Scholar]
- Gumulec, J.; Masarik, M.; Adam, V.; Eckschlager, T.; Provaznik, I.; Kizek, R. Serum and tissue zinc in epithelial malignancies: A meta-analysis. PLoS ONE 2014, 9, e99790. [Google Scholar] [CrossRef]
- Jouybari, L.; Kiani, F.; Akbari, A.; Sanagoo, A.; Sayehmiri, F.; Aaseth, J.; Chartrand, M.S.; Sayehmiri, K.; Chirumbolo, S.; Bjørklund, G. A meta-analysis of zinc levels in breast cancer. J. Trace Elem. Med. Biol. 2019, 56, 90–99. [Google Scholar] [CrossRef] [PubMed]
- Shahrokhi Nejad, S.; Golzari, Z.; Zangiabadian, M.; Salehi Amniyeh Khozani, A.A.; Ebrahimi, R.; Nejadghaderi, S.A.; Aletaha, A. The association between zinc and prostate cancer development: A systematic review and meta-analysis. PLoS ONE 2024, 19, e0299398. [Google Scholar] [CrossRef] [PubMed]
- Hoppe, C.; Kutschan, S.; Dörfler, J.; Büntzel, J.; Büntzel, J.; Huebner, J. Zinc as a complementary treatment for cancer patients: A systematic review. Clin. Exp. Med. 2021, 21, 297–313. [Google Scholar] [CrossRef]
- Gillespie, S.; Kevin, J.; Mason, J. Controlling iron deficiency. In ACC/SCN State-of-the-Art Series Nutrition Policy Discussion Paper; United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition: Geneva, Switzerland, 1991. [Google Scholar]
- Nestel, P.; Nalubola, R. Manual for wheat flour fortification with iron. In Part 1: Guidelines for the Development, Implementation, Monitoring, and Evaluation of a Program for Wheat Flour Fortification with Iron; MOST/USAID: Arlington, VA, USA, 2000. [Google Scholar]
- Ceballos-Rasgado, M.; Brazier, A.K.M.; Gupta, S.; Moran, V.H.; Pierella, E.; Fekete, K.; Lowe, N.M. Methods of Assessment of Zinc Status in Humans: An Updated Review and Meta-analysis. Nutr. Rev. 2025, 83, e778–e800. [Google Scholar] [CrossRef] [PubMed]
- Sudhakar, P.; Latha, P.; Reddy, P.V. Chapter 17—Analytical Techniques. In Phenotyping Crop Plants for Physiological and Biochemical Traits; Sudhakar, P., Latha, P., Reddy, P.V., Eds.; Academic Press: Cambridge, MA, USA, 2016; pp. 137–149. [Google Scholar]
- Pal, A.; Chatterjee, N.; Aaqib, M.; Isha, S.; Aninda, R.; Vincenzo, D.; Mauro, T.; Gianluca, R.; Kalyan, R.; Rosanna, G.; et al. Serum zinc status of patients with colorectal cancer: A systematic review and meta-analysis. J. Trace Elem. Miner. 2024, 9, 100185. [Google Scholar] [CrossRef]
- Poo, J.L.; Romero, R.R.; Robles, J.A.; Montemayor, A.C.; Isoard, F.; Estanes, A.; Uribe, M. Diagnostic value of the copper/zinc ratio in digestive cancer: A case control study. Arch. Med. Res. 1997, 28, 259–263. [Google Scholar]
- International Zinc Nutrition Consultative Group (IZiNCG); Brown, K.H.; Rivera, J.A.; Bhutta, Z.; Gibson, R.S.; King, J.C.; Lönnerdal, B.; Ruel, M.T.; Sandtröm, B.; Wasantwisut, E.; et al. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr. Bull. 2004, 25, S99–S203. [Google Scholar]
- Kaslow, J.E. Copper/Zinc Imbalance; Medical Board of California: Sacramento, CA, USA, 2011.
- Balay, K.S.; Hawthorne, K.M.; Hicks, P.D.; Chen, Z.; Griffin, I.J.; Abrams, S.A. Low Zinc Status and Absorption Exist in Infants with Jejunostomies or Ileostomies Which Persist after Intestinal Repair. Nutrients 2012, 4, 1273–1281. [Google Scholar] [CrossRef] [PubMed]
- Xia, M.; Zang, J.; Wang, Z.; Wang, J.; Wu, Y.; Liu, M.; Shi, Z.; Song, Q.; Cui, X.; Jia, X.; et al. Thyroid cancer and its associations with dietary quality in a 1:1 matched case-control study. Br. J. Nutr. 2023, 129, 283–291. [Google Scholar] [CrossRef] [PubMed]
- Soares, A.A.; Nagashima, Y.G.; Alves, C.X.; de Medeiros, K.S.; Lopes, M.M.G.D.; Brandão-Neto, J. Zinc and thyroid cancer: A systematic review and meta-analysis protocol. PLoS ONE 2024, 19, e0307617. [Google Scholar] [CrossRef]


| First Author | Year of Publication | Country/Continent | Type of Study | n (Cases/ Controls) | Mean (SD) Age (Cases/Controls) | TC Type | TC Serum Zn (Mean ± SD) | Controls Serum Zn (Mean ± SD) | Zn Measurement Method | Total Score (NOS) |
|---|---|---|---|---|---|---|---|---|---|---|
| Ma Q [12] | 2024 | China | CS | 294/- | 46.62/NA | TC | 13.9 μmol/L | 14.2 μmol/L | The automatic biochemical analyzer | 8 |
| Stojsavljević A [13] | 2021 | Serbia | CC | 66/65 | 40/40 | PTC | 1613 ng/g ± 376.46 | 5147 ng/g ± 1130 | ICP-MS | 7 |
| Kazi Tani LS [14] | 2021 | Africa | CC | 46/50 | 40/43 | PTC | 942.1 μg/dL | 1027.9 μg/dL | TXRF | 9 |
| Bibi K and Shah MH [16] | 2020 | Pakistan | CC | 110/108 | 48.5/48.1 | ATC/MTC/ FTC/PTC | 1008 μg/dL ± 0.875 | 1488 μg/dL ± 0.701 * | AAS | 9 |
| Rezaei M [26] | 2019 | Iran | CC | 11/33 | 37/39.39 | TC | 15.6 μg/g ± 5.2 | 66.7 μg/g ± 49.9 | ICP-MS | 7 |
| Emami A [33] | 2017 | Iran | CS | 40/40 | 40—49/NA | MTC | 89.45 μg/dL ± 4.70 | 94.13 μg/dL ± 10.65 | enzyme immunosorbent | 7 |
| Baltaci [17] | 2017 | Türkiye | CC | 30/20 | 50 ± 5/ND | MTC | Male: 65.5 μg/dL ± 6.8 Woman: 66.2 μg/dL ± 7.2 | Male: 98.5 μg/dL ± 11.4 Female: 92.7 μg/dL ± 10.2 | ICS-AES | 8 |
| Chung [34] | 2016 | Korea | CS | 92/- | 43.6/NA | PTC | 60.19 μg/dL ± 6.58 | - | ICP-MS | 6 |
| Przybylik-Mazurek [32] | 2011 | Poland | CC | 38/20 |
PTC: 51.6 FTC: 52.5/37.7 | PTC/FTC | PTC: 12.2 μM/L ± 2.1 FTC: 12.0 μM/L ± 2.1 | 12.5 μM/L ± 2.8 | AAS | 6 |
| Al-Sayer H [18] | 2004 | Kuwait | CC | 43/23 | 33.4/18—53 | PTC/FTC | PTC: 822 μg/L ± 92 FTC: 727 μg/L ± 113 | 1010 μg/L ± 20 | AAS | 8 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Soares, A.A.; Nagashima, Y.G.; Piuvezam, G.; Alves, C.X.; Medeiros, K.S.d.; Lopes, M.M.G.D.; Brandao-Neto, J. Zinc Status and Occurrence of Thyroid Cancer: Systematic Review and Meta-Analysis. Nutrients 2025, 17, 2820. https://doi.org/10.3390/nu17172820
Soares AA, Nagashima YG, Piuvezam G, Alves CX, Medeiros KSd, Lopes MMGD, Brandao-Neto J. Zinc Status and Occurrence of Thyroid Cancer: Systematic Review and Meta-Analysis. Nutrients. 2025; 17(17):2820. https://doi.org/10.3390/nu17172820
Chicago/Turabian StyleSoares, Aline Alves, Yasmin Guerreiro Nagashima, Grasiela Piuvezam, Camila Xavier Alves, Kleyton Santos de Medeiros, Márcia Marília Gomes Dantas Lopes, and Jose Brandao-Neto. 2025. "Zinc Status and Occurrence of Thyroid Cancer: Systematic Review and Meta-Analysis" Nutrients 17, no. 17: 2820. https://doi.org/10.3390/nu17172820
APA StyleSoares, A. A., Nagashima, Y. G., Piuvezam, G., Alves, C. X., Medeiros, K. S. d., Lopes, M. M. G. D., & Brandao-Neto, J. (2025). Zinc Status and Occurrence of Thyroid Cancer: Systematic Review and Meta-Analysis. Nutrients, 17(17), 2820. https://doi.org/10.3390/nu17172820

