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The Inverse Association of Serum Magnesium with Papillary Thyroid Cancer in Thyroid Nodules: a Cross-Sectional Survey Based on Thyroidectomy Population

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Abstract

Magnesium is considered to play a role in preventing cancer. However, the association between serum magnesium and papillary thyroid cancer (PTC) remains unknown. We retrospectively reviewed records of all patients who underwent thyroidectomy with thyroid nodules confirmed pathologically as benign nodule or PTC at our institution from January 2016 to December 2020. Data including demographic characteristics, laboratory tests, and pathological features were analyzed in 5709 adult patients eventually. The subjects with benign nodules had a higher mean serum magnesium level than those with PTC (P < 0.001), and the proportions of PTCs decreased across quartiles of serum magnesium within the normal range. After adjustment for confounders, patients with the lowest quartile of serum magnesium had a higher prevalence of PTC than those with the highest quartile (OR = 1.421, 95%CI: 1.125–1.795, P for trend = 0.005), and the risk of PTC was 0.863 (95%CI: 0.795–0.936) for a per-SD change in serum magnesium. The contribution of serum magnesium remained in subgroup analysis (P for interaction for all analyses > 0.05). Based on the ROC curve, the cut-off value of serum magnesium used to differentiate benign nodules from PTCs was 935 μmol/L. Combining serum magnesium with other clinical indicators can improve the efficacy of predicting PTC. Our results showed that lower serum magnesium within the normal range was associated with a greater risk of PTC among patients with thyroid nodules considering thyroidectomy. Serum magnesium may be an independent protective factor against PTC and provide additional information on the odds of malignancy in uncertain thyroid nodules in combination with other clinical factors.

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Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

References

  1. Kim J, Gosnell JE, Roman SA (2020) Geographic influences in the global rise of thyroid cancer. Nat Rev Endocrinol 16(1):17–29. https://doi.org/10.1038/s41574-019-0263-x

    Article  PubMed  Google Scholar 

  2. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM (2017) Trends in thyroid cancer incidence and mortality in the united states, 1974–2013. JAMA 317(13):1338–1348. https://doi.org/10.1001/jama.2017.2719

    Article  PubMed  PubMed Central  Google Scholar 

  3. Morris LG, Myssiorek D (2010) Improved detection does not fully explain the rising incidence of well-differentiated thyroid cancer: a population-based analysis. Am J Surg 200(4):454–461. https://doi.org/10.1016/j.amjsurg.2009.11.008

    Article  PubMed  PubMed Central  Google Scholar 

  4. Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS (2018) The diagnosis and management of thyroid nodules: a review. JAMA 319(9):914–924. https://doi.org/10.1001/jama.2018.0898

    Article  PubMed  Google Scholar 

  5. de Baaij JH, Hoenderop JG, Bindels RJ (2015) Magnesium in man: implications for health and disease. Physiol Rev 95(1):1–46. https://doi.org/10.1152/physrev.00012.2014

    Article  CAS  PubMed  Google Scholar 

  6. Dai Q, Motley SS, Smith JA Jr et al (2011) Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer. PLoS One 6(4):e18237. https://doi.org/10.1371/journal.pone.0018237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Polter EJ, Onyeaghala G, Lutsey PL et al (2019) Prospective association of serum and dietary magnesium with colorectal cancer incidence. Cancer Epidemiol Biomarkers Prev 28(8):1292–1299. https://doi.org/10.1158/1055-9965.Epi-18-1300

    Article  CAS  PubMed  Google Scholar 

  8. Yu G, Hsu WL, Coghill AE et al (2019) Whole-exome sequencing of nasopharyngeal carcinoma families reveals novel variants potentially involved in nasopharyngeal carcinoma. Sci Rep 9(1):9916. https://doi.org/10.1038/s41598-019-46137-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shahy EM, Taha MM, Ibrahim KS (2020) Assessment of ykl-40, lipid profile, antioxidant status, and some trace elements in benign and malignant breast proliferation. Mol Biol Rep 47(9):6973–6982. https://doi.org/10.1007/s11033-020-05756-1

    Article  CAS  PubMed  Google Scholar 

  10. Bezerra DLC, Mendes PMV, Melo SRS et al (2021) Hypomagnesemia and its relationship with oxidative stress markers in women with breast cancer. Biol Trace Elem Res 199(12):4466–4474. https://doi.org/10.1007/s12011-021-02579-4

    Article  CAS  PubMed  Google Scholar 

  11. Meng Y, Sun J, Yu J, Wang C, Su J (2019) Dietary intakes of calcium, iron, magnesium, and potassium elements and the risk of colorectal cancer: a meta-analysis. Biol Trace Elem Res 189(2):325–335. https://doi.org/10.1007/s12011-018-1474-z

    Article  CAS  PubMed  Google Scholar 

  12. Song X, Zhong X, Tang K, Wu G, Jiang Y (2018) Serum magnesium levels and lung cancer risk: a meta-analysis. World J Surg Oncol 16(1):137. https://doi.org/10.1186/s12957-018-1447-x

    Article  PubMed  PubMed Central  Google Scholar 

  13. Leung PL, Li XL (1996) Multielement analysis in serum of thyroid cancer patients before and after a surgical operation. Biol Trace Elem Res 51(3):259–266. https://doi.org/10.1007/bf02784080

    Article  CAS  PubMed  Google Scholar 

  14. Al-Sayer H, Mathew TC, Asfar S et al (2004) Serum changes in trace elements during thyroid cancers. Mol Cell Biochem 260(1–2):1–5. https://doi.org/10.1023/b:mcbi.0000026027.20680.c7

    Article  CAS  PubMed  Google Scholar 

  15. Xing M (2012) Oxidative stress: a new risk factor for thyroid cancer. Endocr Relat Cancer 19(1):C7-11. https://doi.org/10.1530/erc-11-0360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lassoued S, Mseddi M, Mnif F et al (2010) A comparative study of the oxidative profile in graves’ disease, Hashimoto’s thyroiditis, and papillary thyroid cancer. Biol Trace Elem Res 138(1–3):107–115. https://doi.org/10.1007/s12011-010-8625-1

    Article  CAS  PubMed  Google Scholar 

  17. Wang D, Feng JF, Zeng P, Yang YH, Luo J, Yang YW (2011) Total oxidant/antioxidant status in sera of patients with thyroid cancers. Endocr Relat Cancer 18(6):773–782. https://doi.org/10.1530/erc-11-0230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ameziane El Hassani R, Buffet C, Leboulleux S, Dupuy C (2019) Oxidative stress in thyroid carcinomas: Biological and clinical significance. Endocr Relat Cancer 26(3):R131-r143. https://doi.org/10.1530/erc-18-0476

    Article  CAS  PubMed  Google Scholar 

  19. Jia X, Pang P, Wang L et al (2020) Clinical analysis of preoperative anti-thyroglobulin antibody in papillary thyroid cancer between 2011 and 2015 in Beijing, China: a retrospective study. Front Endocrinol (Lausanne) 11:452. https://doi.org/10.3389/fendo.2020.00452

    Article  PubMed  Google Scholar 

  20. Kim ES, Lim DJ, Baek KH et al (2010) Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 20(8):885–891. https://doi.org/10.1089/thy.2009.0384

    Article  CAS  PubMed  Google Scholar 

  21. Rago T, Fiore E, Scutari M et al (2010) Male sex, single nodularity, and young age are associated with the risk of finding a papillary thyroid cancer on fine-needle aspiration cytology in a large series of patients with nodular thyroid disease. Eur J Endocrinol 162(4):763–770. https://doi.org/10.1530/eje-09-0895

    Article  CAS  PubMed  Google Scholar 

  22. Schmid D, Ricci C, Behrens G, Leitzmann MF (2015) Adiposity and risk of thyroid cancer: a systematic review and meta-analysis. Obes Rev 16(12):1042–1054. https://doi.org/10.1111/obr.12321

    Article  CAS  PubMed  Google Scholar 

  23. Haymart MR, Repplinger DJ, Leverson GE et al (2008) Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 93(3):809–814. https://doi.org/10.1210/jc.2007-2215

    Article  CAS  PubMed  Google Scholar 

  24. Wang K, Wei H, Zhang W et al (2018) Severely low serum magnesium is associated with increased risks of positive anti-thyroglobulin antibody and hypothyroidism: a cross-sectional study. Sci Rep 8(1):9904. https://doi.org/10.1038/s41598-018-28362-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ehlers M, Schott M (2014) Hashimoto’s thyroiditis and papillary thyroid cancer: Are they immunologically linked? Trends Endocrinol Metab 25(12):656–664. https://doi.org/10.1016/j.tem.2014.09.001

    Article  CAS  PubMed  Google Scholar 

  26. Uhliarova B, Hajtman A (2018) Hashimoto’s thyroiditis - an independent risk factor for papillary carcinoma. Braz J Otorhinolaryngol 84(6):729–735. https://doi.org/10.1016/j.bjorl.2017.08.012

    Article  PubMed  Google Scholar 

  27. Pan J, Ye F, Yu C et al (2021) Papillary thyroid carcinoma landscape and its immunological link with hashimoto thyroiditis at single-cell resolution. Front Cell Dev Biol 9:758339. https://doi.org/10.3389/fcell.2021.758339

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hartwig A (2001) Role of magnesium in genomic stability. Mutat Res 475(1–2):113–121. https://doi.org/10.1016/s0027-5107(01)00074-4

    Article  CAS  PubMed  Google Scholar 

  29. Yang L, Arora K, Beard WA, Wilson SH, Schlick T (2004) Critical role of magnesium ions in DNA polymerase beta’s closing and active site assembly. J Am Chem Soc 126(27):8441–8453. https://doi.org/10.1021/ja049412o

    Article  CAS  PubMed  Google Scholar 

  30. Wolf FI, Maier JA, Nasulewicz A et al (2007) Magnesium and neoplasia: from carcinogenesis to tumor growth and progression or treatment. Arch Biochem Biophys 458(1):24–32. https://doi.org/10.1016/j.abb.2006.02.016

    Article  CAS  PubMed  Google Scholar 

  31. Morais JB, Severo JS, Santos LR et al (2017) Role of magnesium in oxidative stress in individuals with obesity. Biol Trace Elem Res 176(1):20–26. https://doi.org/10.1007/s12011-016-0793-1

    Article  CAS  PubMed  Google Scholar 

  32. Klatka M, Grywalska E, Partyka M, Charytanowicz M, Rolinski J (2013) Impact of methimazole treatment on magnesium concentration and lymphocytes activation in adolescents with graves’ disease. Biol Trace Elem Res 153(1–3):155–170. https://doi.org/10.1007/s12011-013-9690-z

    Article  CAS  PubMed  Google Scholar 

  33. Laughlin MR, Thompson D (1996) The regulatory role for magnesium in glycolytic flux of the human erythrocyte. J Biol Chem 271(46):28977–28983. https://doi.org/10.1074/jbc.271.46.28977

    Article  CAS  PubMed  Google Scholar 

  34. Kostov K (2019) Effects of magnesium deficiency on mechanisms of insulin resistance in type 2 diabetes: focusing on the processes of insulin secretion and signaling. Int J Mol Sci 20(6). https://doi.org/10.3390/ijms20061351

  35. Pazaitou-Panayiotou K, Polyzos SA, Mantzoros CS (2013) Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms. Obes Rev 14(12):1006–1022. https://doi.org/10.1111/obr.12070

    Article  CAS  PubMed  Google Scholar 

  36. Yin DT, He H, Yu K et al (2018) The association between thyroid cancer and insulin resistance, metabolic syndrome and its components: a systematic review and meta-analysis. Int J Surg 57:66–75. https://doi.org/10.1016/j.ijsu.2018.07.013

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank the staff of the First Medical Center of Chinese PLA General Hospital, Beijing, China, for their participation in this study.

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Authors and Affiliations

  1. Department of Endocrinology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, 100853, Beijing, China

    Huaijin Xu, Xiaodong Hu, Jiefei Li, Zhimei Nie, Shaoyang Kang, Hongzhou Liu, Yuhan Wang & Zhaohui Lyu

  2. School of Medicine, Nankai University, Tianjin, 300071, China

    Huaijin Xu, Jiefei Li & Zhaohui Lyu

  3. Center for Endocrine Metabolism and Immune Disease, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China

    Xiaomeng Jia

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  1. Huaijin Xu
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Contributions

Conception and design: Zhaohui Lyu. Material preparation: Xiaomeng Jia. Data collection: Huaijin Xu, Xiaodong Hu, Jiefei Li, Zhimei Nie, and Shaoyang Kang. Analysis and interpretation of data: Huaijin Xu. Validation: Xiaodong Hu, Hongzhou Liu, and Yuhan Wang.

Writing the original draft: Huaijin Xu. Revising the manuscript: Zhaohui Lyu.

Corresponding author

Correspondence to Zhaohui Lyu.

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The study was conducted in line with the Helsinki Declaration and approved by the Ethics Committee of Chinese PLA General Hospital (No.S2022-0115–01) with waived informed consent considering the collection of de-identified retrospective data.

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The authors declare no competing interests.

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Xu, H., Hu, X., Li, J. et al. The Inverse Association of Serum Magnesium with Papillary Thyroid Cancer in Thyroid Nodules: a Cross-Sectional Survey Based on Thyroidectomy Population. Biol Trace Elem Res 201, 3279–3289 (2023). https://doi.org/10.1007/s12011-022-03448-4

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