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Nutrition and Health (including climate and ecological aspects)

Histopathological prognosis of papillary thyroid carcinoma associated with nutritional status of vitamins A and E

European Journal of Clinical Nutrition volume 76, pages 469–476 (2022)Cite this article

Subjects

Abstract

Background/Objectives

Experimental and clinical studies have shown that vitamins A and E can inhibit cancer formation and progression. The unfavourable status of these vitamins can represent risk factors for the disease. This study aimed to evaluate the associations between the nutritional status of vitamins A and E (serum levels and dietary intake) and histopathological outcomes in Papillary Thyroid Carcinoma (PTC) patients.

Subjects/Methods

We applied a cross-sectional study (2017–2018) and quantified retinol (ROH) and α-tocopherol (TOH) serum levels and vitamins dietary intake of 46 PTC patients. Serum vitamins were quantified by high efficiency liquid chromatography and vitamins dietary intake was analyzed by 24‐hr dietary recalls.

Results

Patients with lower ROH serum levels were more likely to present lymph node metastasis and/or angiolymphatic invasion (p = 0.025). In addition, higher vitamin A and vitamin E intake are related to the absence of extrathyroidal extension (p = 0.013) and lymph node metastasis (p = 0.007), respectively. Our findings suggest that a ROH serum level greater than 2.65 μmol/L in PTC patients may be a protective factor against the presence of lymph node metastasis and angiolymphatic invasion. In addition, vitamin A and E intake may protect against extrathyroidal extension and lymph node metastasis.

Conclusions

A favourable nutritional status (higher serum levels and/or intake) of vitamin A and E may be associated with less aggressive tumours in PTC patients.

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Fig. 1
Fig. 2: Serum ROH concentration in patients with PTC and association between the five histopathological features.
Fig. 3: Vitamin A intake in patients with PTC and association between the five histopathological features.
Fig. 4: Serum TOH concentration in patients with PTC and association between the five histopathological features.
Fig. 5: Vitamin A intake in patients with PTC and association between the five histopathological features.

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References

  1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Pineros M, et al. Cancer Today (powered by GLOBOCAN 2018). IARC CancerBase; 2018.

  2. Boufraqech M, Patel D, Xiong Y, Kebebew E. Diagnosis of thyroid cancer: state of art. Expert Opin Med Diagn. 2013;7:331–42.

    Article  PubMed  Google Scholar 

  3. Gou Q, Gao L, Nie X, Pu W, Zhu J, Wang Y, et al. Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated CDKN1a expression in papillary thyroid carcinoma. Cancer Res. 2018;78:4163–74.

    Article  CAS  PubMed  Google Scholar 

  4. Maksimovic S, Jakovljevic B, Gojkovic Z. Lymph node metastases papillary thyroid carcinoma and their importance in recurrence of disease. Med Arch (Sarajevo, Bosnia Herzeg). 2018;72:108–11.

    Google Scholar 

  5. Sun Y, Lv H, Zhang S, Bai Y, Shi B. Gender-specific risk of central compartment lymph node metastasis in papillary thyroid carcinoma. Int J Endocrinol. 2018;2018:6710326.

    PubMed  PubMed Central  Google Scholar 

  6. Macejová D, Galbavý S, Podoba J, Bialešová L, Brtko J. mRNA expression pattern of retinoic acid and retinoid X nuclear receptor subtypes in human thyroid papillary carcinoma. Oncol Rep. 2013;30:2371–8.

    Article  PubMed  CAS  Google Scholar 

  7. Emami A, Nazem MR, Shekarriz R, Hedayati M. Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary thyroid carcinoma: a cross-sectional study. Nutrition. 2017;41:86–9.

    Article  CAS  PubMed  Google Scholar 

  8. Lawal AO, Kolude B, Adeyemi BF, Lawoyin JO, Akang EE. Serum antioxidant vitamins and the risk of oral cancer in patients seen at a tertiary institution in Nigeria. Niger J Clin Pr. 2012;15:30–3.

    Article  CAS  Google Scholar 

  9. Lima L, de Melo TCT, Marques D, de Araújo JNG, Leite ISF, Alves CX, et al. Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review. BMC Cancer. 2019;19:866.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Mamede AC, Tavares SD, Abrantes AM, Trindade J, Maia JM, Botelho MF. The role of vitamins in cancer: a review. Nutr Cancer. 2011;63:479–94.

    Article  CAS  PubMed  Google Scholar 

  11. Nash SH, Till C, Song X, Lucia MS, Parnes HL, Thompson IM Jr, et al. Serum retinol and carotenoid concentrations and prostate cancer risk: results from the prostate cancer prevention trial. Cancer Epidemiol Biomark Prev. 2015;24:1507–15.

    Article  Google Scholar 

  12. Huang J, Panagiotou OA, Anic GM, Mondul AM, Liao LM, Derkach A, et al. Metabolomic profiling of serum retinol in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. Sci Rep. 2017;7:10601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Mondul AM, Watters JL, Männistö S, Weinstein SJ, Snyder K, Virtamo J, et al. Serum retinol and risk of prostate cancer. Am J Epidemiol. 2011;173:813–21.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Larouche D, Hanna M, Chang S-L, Jacob S, Têtu B, Diorio C. Evaluation of antioxidant intakes in relation to inflammatory markers expression within the normal breast tissue of breast cancer patients. Integr Cancer Ther. 2017;16:485–95.

    Article  CAS  PubMed  Google Scholar 

  15. Oh SW, Moon S, Park DJ, Cho BY, Jung KC, Lee DS, et al. Combined therapy with 131I and retinoic acid in Korean patients with radioiodine-refractory papillary thyroid cancer. Eur J Nucl Med Mol Imaging. 2011;38:1798–805.

    Article  CAS  PubMed  Google Scholar 

  16. Sailo BL, Banik K, Padmavathi G, Javadi M, Bordoloi D, Kunnumakkara AB. Tocotrienols: the promising analogues of vitamin E for cancer therapeutics. Pharm Res. 2018;130:259–72.

    Article  CAS  Google Scholar 

  17. Sato C, Kaneko S, Sato A, Virgona N, Namiki K, Yano T. Combination effect of δ-Tocotrienol and γ-Tocopherol on prostate cancer cell growth. J Nutr Sci Vitaminol (Tokyo). 2017;63:349–54.

    Article  CAS  Google Scholar 

  18. Jiang Q. Natural forms of vitamin E as effective agents for cancer prevention and therapy. Adv Nutr. 2017;8:850–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zaballos MA, Santisteban P. Key signaling pathways in thyroid cancer. J Endocrinol. 2017;235:R43–61.

    Article  CAS  PubMed  Google Scholar 

  20. Faul F, Erdfelder E, Buchner A, Lang A-G. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41:1149–60.

    Article  PubMed  Google Scholar 

  21. Tuttle RM, Haugen B, Perrier ND. Updated American Joint Committee on cancer/tumor-node-metastasis staging system for differentiated and anaplastic thyroid cancer (eighth edition): what changed and why? Thyroid. 2017;27:751–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ortega RM, López-Sobaler AM, Martínez RM, Andrés P, Quintas ME. Influence of smoking on vitamin E status during the third trimester of pregnancy and on breast-milk tocopherol concentrations in Spanish women. Am J Clin Nutr. 1998;68:662–7.

    Article  CAS  PubMed  Google Scholar 

  23. Nierenberg DW, Nann SL. A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples. Am J Clin Nutr. 1992;56:417–26.

    Article  CAS  PubMed  Google Scholar 

  24. Kabat GC, Kim MY, Sarto GE, Shikany JM, Rohan TE. Repeated measurements of serum carotenoid, retinol and tocopherol levels in relation to colorectal cancer risk in the Women’s Health Initiative. Eur J Clin Nutr. 2012;66:549–54.

    Article  CAS  PubMed  Google Scholar 

  25. Morimoto Y, Ollberding NJ, Cooney RV, Wilkens LR, Franke AA, Le Marchand L, et al. Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2013;22:2075 LP–2083.

    Article  CAS  Google Scholar 

  26. McDonald AC, Bunker CH, Raman J, Richie J, Patrick AL. Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high prostate cancer risk in comparison with African-American men. Br J Nutr. 2017;117:1128–36.

    Article  CAS  PubMed  Google Scholar 

  27. SAT. priorities in the assessment of vitamin a and iron status in populations. Biomarkers of vitamin A status: what do they mean? Geneva; 2012.

  28. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. 2000. https://doi.org/10.17226/9810.

  29. Thompson FE, Byers T. Dietary assessment resource manual. J Nutr. 1994;124:2245S–317S.

    CAS  PubMed  Google Scholar 

  30. Instituto Brasileiro de Geografia e Estatística. Pesquisa de orçamentos familiares 2008–9: quadro de medidas para alimentação Brasil; 2011.

  31. USDA. National Nutrient Database for Standard Reference.

  32. Harttig U, Haubrock J, Knüppel S, Boeing H. The MSM program: web-based statistics package for estimating usual dietary intake using the Multiple Source Method. Eur J Clin Nutr. 2011;65:S87–91.

    Article  PubMed  Google Scholar 

  33. Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. In: American Journal of Clinical Nutrition; 1997. https://doi.org/10.1093/ajcn/65.4.1220S.

  34. Shklar G, Schwartz J. Oral cancer inhibition by micronutrients. The experimental basis for clinical trials. Eur J Cancer B Oral Oncol. 1993;29B:9–16.

    Article  CAS  PubMed  Google Scholar 

  35. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington, DC; 2007.

  36. Lan L, Cui D, Luo Y, Shi BY, Deng LL, Zhang GY, et al. Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro. J Endocrinol Invest. 2009;32:731–8.

    Article  CAS  PubMed  Google Scholar 

  37. Grünwald F, Pakos E, Bender H, Menzel C, Otte R, Palmedo H, et al. Redifferentiation therapy with retinoic acid in follicular thyroid cancer. J Nucl Med. 1998;39:1555 LP–8.

    Google Scholar 

  38. Hoffmann S, Rockenstein A, Ramaswamy A, Celik I, Wunderlich A, Lingelbach S, et al. Retinoic acid inhibits angiogenesis and tumor growth of thyroid cancer cells. Mol Cell Endocrinol. 2007;264:74–81.

    Article  CAS  PubMed  Google Scholar 

  39. Kim WG, Kim EY, Kim TY, Ryu J-S, Hong SJ, Kim WB, et al. Redifferentiation therapy with 13-cis retinoic acids in radioiodine-resistant thyroid cancer. Endocr J. 2009;56:105–12.

    Article  CAS  PubMed  Google Scholar 

  40. Schmutzler C, Köhrle J. Retinoic acid redifferentiation therapy for thyroid cancer. Thyroid. 2000;10:393–406.

    Article  CAS  PubMed  Google Scholar 

  41. Li Y-T, Tian X-T, Wu M-L, Zheng X, Kong Q-Y, Cheng X-X, et al. Resveratrol suppresses the growth and enhances retinoic acid sensitivity of anaplastic thyroid cancer cells. Int J Mol Sci. 2018; 19. https://doi.org/10.3390/ijms19041030.

  42. Van Herle AJ, Agatep ML, Padua DN 3rd, Totanes TL, Canlapan DV, Van Herle HM, et al. Effects of 13 cis-retinoic acid on growth and differentiation of human follicular carcinoma cells (UCLA R0 82 W-1) in vitro. J Clin Endocrinol Metab. 1990;71:755–63.

    Article  PubMed  Google Scholar 

  43. Simon D, Körber C, Krausch M, Segering J, Groth P, Görges R, et al. Clinical impact of retinoids in redifferentiation therapy of advanced thyroid cancer: final results of a pilot study. Eur J Nucl Med Mol Imaging. 2002;29:775–82.

    Article  CAS  PubMed  Google Scholar 

  44. Cristiano MC, Cosco D, Celia C, Tudose A, Mare R, Paolino D, et al. Anticancer activity of all-trans retinoic acid-loaded liposomes on human thyroid carcinoma cells. Colloids Surf B Biointerfaces. 2017;150:408–16.

    Article  CAS  PubMed  Google Scholar 

  45. D’Avanzo B, Ron E, La Vecchia C, Francaschi S, Negri E, Zleglar R. Selected micronutrient intake and thyroid carcinoma risk. Cancer. 1997;79:2186–92.

    Article  PubMed  Google Scholar 

  46. Silalahi J. Anticancer and health protective properties of citrus fruit components. Asia Pac J Clin Nutr. 2002;11:79–84.

    Article  CAS  PubMed  Google Scholar 

  47. Senthil N, Manoharan S. Lipid peroxidation and antioxidants status in patients with papillary thyroid carcinoma in India. Asia Pac J Clin Nutr. 2004;13:391–5.

    CAS  PubMed  Google Scholar 

  48. Yang H, Xu M, Lu F, Zhang Q, Feng Y, Yang CS, et al. Tocopherols inhibit esophageal carcinogenesis through attenuating NF-κB activation and CXCR3-mediated inflammation. Oncogene. 2018;37:3909–23.

    Article  CAS  PubMed  Google Scholar 

  49. Seidman MD, Quirk WS, Shirwany NA. Reactive oxygen metabolites, antioxidants and head and neck cancer. Head Neck. 1999;21:467–79.

    Article  CAS  PubMed  Google Scholar 

  50. Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, et al. Vitamin E: emerging aspects and new directions. Free Radic Biol Med. 2017;102:16–36.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The researchers would like to thank the team of professionals of the Liga Norte-Riograndense Contra o Câncer.

Funding

This study was partly financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.

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Author notes

  1. These authors contributed equally: Lara Lima-Antoine, Julianna Lys de Sousa Alves Neri.

Authors and Affiliations

  1. Postgraduate Program of Nutrition, Federal University of Rio Grande do Norte, Natal, Brazil

    Lara Lima-Antoine, Julianna Lys de Sousa Alves Neri, Ana Gabriella da Costa Lemos Silva, Clélia de Oliveira Lyra, Karla Danielly da Silva Ribeiro & Vivian Nogueira Silbiger

  2. Sorbonne Université, Inserm UMRS_938, Centre de Recherche Saint-Antoine, Paris, France

    Lara Lima-Antoine

  3. Laboratory of Bioanalysis and Molecular Biotechnology, Federal University of Rio Grande do Norte, Natal, Brazil

    Thaisa Cristina Tavares de Melo & Isabela Samária Fernandes Leite

  4. Postgraduate Program of genetics and molecular biology, Federal University of Pará, Belém, Brazil

    Diego Marques da Costa Santos

  5. Northeast Biotechnology Network (RENORBIO), Graduate Program in Biotechnology, Federal University of Rio Grande do Norte, Natal, Brazil

    Jéssica Nayara Góes de Araújo, Andre Ducati Luchessi & Vivian Nogueira Silbiger

  6. Postgraduate Program of Healthy Sciences, Federal University of Rio Grande do Norte, Natal, Brazil

    Nathália Kelly de Araújo & Andre Ducati Luchessi

  7. Division of Pathology, Hospital Liga Norte Riograndense Contra o Câncer, Natal, Brazil

    Carlos C. de Oliveira Ramos

  8. Division of Head and Neck Surgery, Liga Norte Riograndense Contra o Câncer Hospital, Natal, Brazil

    Sheila Ramos de Miranda Henriques Tarrapp

  9. Postgraduate Program of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil

    Andre Ducati Luchessi & Vivian Nogueira Silbiger

  10. Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Brazil

    Andre Ducati Luchessi & Vivian Nogueira Silbiger

Authors
  1. Lara Lima-Antoine
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Contributions

LLA and JLSAN contributed equally to this work. LLA and JLSAN collected the data and wrote the first draft with contributions from NKA, KDSR, AGCLS, TCTM, ISFL, COL and VNS. ADL did the statistical analysis. DM and JNGA contributed with figures elaboration. CCOR and SRMHT provided technical assistance and histological evaluation. All authors reviewed and commented on subsequent drafts of the paper.

Corresponding author

Correspondence to Vivian Nogueira Silbiger.

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Lima-Antoine, L., de Sousa Alves Neri, J.L., de Melo, T.C.T. et al. Histopathological prognosis of papillary thyroid carcinoma associated with nutritional status of vitamins A and E. Eur J Clin Nutr 76, 469–476 (2022). https://doi.org/10.1038/s41430-021-00976-5

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  • DOI: https://doi.org/10.1038/s41430-021-00976-5

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