View More View Less
  • 1 Department of Biochemistry, School of Medicine, Ardabil, Iran
  • 2 Department of Immunology, School of Medicine, Tehran, Iran
  • 3 Department of Medical Biochemistry, School of Medicine, Tehran, Iran
  • 4 Department of Immunology, School of Medicine, Tabriz, Iran
  • 5 Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Tehran, Iran
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Abstract

Background

Thyroid cancer is the most common endocrine malignancy. Studies have observed an anti-cancer effect for vitamin D and found that polymorphisms of vitamin D receptors can influence the prevalence of various cancers. The present study investigated the serum level of vitamin D and FokI, BsmI and Tru9I polymorphisms of vitamin D receptors.

Methods

Forty patients with medullary thyroid cancer and 40 healthy controls were investigated. The genomic DNA of the subjects was extracted using saturated salt/proteinase K and investigated by PCR sequencing. Serum levels of vitamin D were evaluated by ELISA. The results were analyzed in SPSS and GraphPad Prism 5 software.

Results

The genotypic and allelic frequencies of FokI and BsmI polymorphisms showed no significant differences between test and control groups. For Tru9I polymorphism, Tt genotype and t allelic frequency in the test group were significantly different from those of the control group. Also, we found Tt genotype and t allelic frequency to be significantly associated with medullary thyroid cancer (MTC) type and the agressiveness of the disease. The average serum vitamin D level was 23.32 ng/mL and 18.95 ng/mL for patients and controls, respectively, and the difference between the two groups was statistically significant. Moreover, we found high serum vitamin D level to be associated with t allelic frequency.

Conclusions

Unexpectedly, the mean serum vitamin D level of the test group was significantly higher than that of the control group. Tru9I polymorphism was found to be significantly correlated with the prevalence of medullary thyroid carcinoma.

  • 1.

    Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, . A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 1997; 12(6): 915921, https://doi.org/10.1359/jbmr.1997.12.6.915.

    • Search Google Scholar
    • Export Citation
  • 2.

    Baier R, Grauer A, Lazaretti-Castro M, Ziegler R, Raue F. Differential effects of 1,25-dihydroxyvitamin D3 on cell proliferation and calcitonin gene expression. Endocrinology 1994; 135(5): 20062011, https://doi.org/10.1210/en.135.5.2006.

    • Search Google Scholar
    • Export Citation
  • 3.

    Carvalho IS, Goncalves CI, Almeida JT, Azevedo T, Martins T, Rodrigues FJ, . Association of Vitamin D Pathway Genetic Variation and Thyroid Cancer. Genes (Basel) 2019; 10(8): 572, https://doi.org/10.3390/genes10080572.

    • Search Google Scholar
    • Export Citation
  • 4.

    Clendenen TV, Arslan AA, Koenig KL, Enquist K, Wirgin I, Agren A, . Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer. Cancer Lett 2008; 260(1-2): 209215, https://doi.org/10.1016/j.canlet.2007.11.002.

    • Search Google Scholar
    • Export Citation
  • 5.

    Clinckspoor I, Verlinden L, Overbergh L, Korch C, Bouillon R, Mathieu C, . 1,25-dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer. J Steroid Biochem Mol Biol 2011; 124: 19, https://doi.org/10.1016/j.jsbmb.2010.12.008.

    • Search Google Scholar
    • Export Citation
  • 6.

    Cote GJ, Rogers DG, Huang ES, Gagel RF. The effect of 1,25-dihydroxyvitamin D3 treatment on calcitonin and calcitonin gene-related peptide mRNA levels in cultured human thyroid C-cells. Biochem Biophys Res Commun 1987; 149(1): 239243, https://doi.org/10.1016/0006-291X(87)91630-5.

    • Search Google Scholar
    • Export Citation
  • 7.

    Doubi A, Al-Qannass A, Al-Angari SS, Al-Qahtani KH, Alessa M, Al-Dhahri S. Trends in thyroid carcinoma among thyroidectomy patients: a 12-year multicenter study. Ann Saudi Med 2019; 39(5): 345349, https://doi.org/10.5144/0256-4947.2019.345.

    • Search Google Scholar
    • Export Citation
  • 8.

    Franssila K, Saxen E, Teppo L, Bjarnason O, Tulinius H, Normann T, . Incidence of different morphological types of thyroid cancer in the Nordic countries. Acta Pathol Microbiol Scand A 1981; 89(1): 4955, https://doi.org/10.1111/j.1699-0463.1981.tb00186.x.

    • Search Google Scholar
    • Export Citation
  • 9.

    Gandini S, Raimondi S, Gnagnarella P, Dore JF, Maisonneuve P, Testori A. Vitamin D and skin cancer: a meta-analysis. Eur J Canc 2009; 45(4): 634641, https://doi.org/10.1016/j.ejca.2008.10.003.

    • Search Google Scholar
    • Export Citation
  • 10.

    Gapska P, Scott RJ, Serrano-Fernandez P, Huzarski T, Byrski T, Kladny J, . Vitamin D receptor variants and breast cancer risk in the Polish population. Breast Canc Res Treat 2009; 115(3): 629633, https://doi.org/10.1007/s10549-008-0107-1.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ghazi AA, Bagheri M, Tabibi A, Sarvghadi F, Abdi H, Hedayati M, . Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies. Arch Iran Med 2014; 17(5): 378382, https://doi.org/0141705/aim.0013.

    • Search Google Scholar
    • Export Citation
  • 12.

    Giovannucci E. Strengths and limitations of current epidemiologic studies: vitamin D as a modifier of colon and prostate cancer risk. Nutr Rev 2007; 65(8 Pt 2): S77S79, https://doi.org/10.1301/nr.2007.aug.S77–S79.

    • Search Google Scholar
    • Export Citation
  • 13.

    Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, . Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med 2007; 32(3): 210216, https://doi.org/10.1016/j.amepre.2006.11.004.

    • Search Google Scholar
    • Export Citation
  • 14.

    Guo H, Guo J, Xie W, Yuan L, Sheng X. The role of vitamin D in ovarian cancer: epidemiology, molecular mechanism and prevention. J Ovarian Res 2018; 11(1): 71, https://doi.org/10.1186/s13048-018-0443-7.

    • Search Google Scholar
    • Export Citation
  • 15.

    Haghpanah V, Ghaffari SH, Rahimpou rP, Abbasi A, Saeedi M, Pak H, . Vitamin D receptor gene polymorphisms in patients with thyroid cancer. Gene Ther Mol Biol 2007; 11: 299304.

    • Search Google Scholar
    • Export Citation
  • 16.

    Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)(2)vitamin D(3): genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 2011; 25(4): 543559, https://doi.org/10.1016/j.beem.2011.05.010.

    • Search Google Scholar
    • Export Citation
  • 17.

    Hedayati M, Yaghmaei P, Pooyamanesh Z, Zarif Yeganeh M, Hoghooghi Rad L. Leptin: a correlated Peptide to papillary thyroid carcinoma? J Thyroid Res 2011; 2011: 832163, https://doi.org/10.4061/2011/832163.

    • Search Google Scholar
    • Export Citation
  • 18.

    Hedayati M, Zarif Yeganeh M, Sheikhol Eslami S, Rezghi Barez S, Hoghooghi Rad L, Azizi F. Predominant RET Germline Mutations in Exons 10, 11, and 16 in Iranian Patients with Hereditary Medullary Thyroid Carcinoma. J Thyroid Res 2011; 2011: 264248, https://doi.org/10.4061/2011/264248.

    • Search Google Scholar
    • Export Citation
  • 19.

    Jabbari S, Hedayati M, Yaghmaei P, Parivar K. Medullary Thyroid Carcinoma--Circulating Status of Vaspin and Retinol Binding Protein-4 in Iranian Patients. Asian Pac J Cancer Prev 2015; 16(15): 65076512, https://doi.org/10.7314/apjcp.2015.16.15.6507.

    • Search Google Scholar
    • Export Citation
  • 20.

    Jeon SM, Shin EA. Exploring vitamin D metabolism and function in cancer. Exp Mol Med 2018; 50(4): 20, https://doi.org/10.1038/s12276-018-0038-9.

    • Search Google Scholar
    • Export Citation
  • 21.

    Jiao J, Li Y, Xu S, Wu J, Yue S, Liu L. Association of FokI, TaqI, BsmI and ApaI polymorphisms with diabetic retinopathy: a pooled analysis of case-control studies. Afr Health Sci 2018; 18(4): 891899, https://doi.org/10.4314/ahs.v18i4.7.

    • Search Google Scholar
    • Export Citation
  • 22.

    Jingwi EY, Abbas M, Ricks-Santi L, Winchester D, Beyene D, Day A, . Vitamin D receptor genetic polymorphisms are associated with PSA level, Gleason score and prostate cancer risk in African-American men. Anticancer Res 2015; 35(3): 15491558.

    • Search Google Scholar
    • Export Citation
  • 23.

    Jonklaas J, Danielsen M, Wang H. A pilot study of serum selenium, vitamin D, and thyrotropin concentrations in patients with thyroid cancer. Thyroid 2013; 23(9): 10791086, https://doi.org/10.1089/thy.2012.0548.

    • Search Google Scholar
    • Export Citation
  • 24.

    Kambale PR, Haldar D, Kabi BC, Kambale KP. Study of Vitamin D Receptor Gene Polymorphism (FokI, TaqI and ApaI) Among Prostate Cancer Patients in North India. J Clin Diagn Res 2017; 11(6): BC05BC08, https://doi.org/10.7860/JCDR/2017/24290.9976.

    • Search Google Scholar
    • Export Citation
  • 25.

    Khadzkou K, Buchwald P, Westin G, Dralle H, Akerstrom G, Hellman P. 25-hydroxyvitamin D3 1alpha-hydroxylase and vitamin D receptor expression in papillary thyroid carcinoma. J Histochem Cytochem 2006; 54(3): 355361, https://doi.org/10.1369/jhc.5A6734.2005.

    • Search Google Scholar
    • Export Citation
  • 26.

    Kurucu N, Sahin G, Sari N, Ceylaner S, Ilhan IE. Association of vitamin D receptor gene polymorphisms with osteosarcoma risk and prognosis. J Bone Oncol 2019; 14: 100208, https://doi.org/10.1016/j.jbo.2018.100208.

    • Search Google Scholar
    • Export Citation
  • 27.

    Laney N, Meza J, Lyden E, Erickson J, Treude K, Goldner W. The prevalence of vitamin D deficiency is similar between thyroid nodule and thyroid cancer patients. Int J Endocrinol Metab 2010; 2010: 805716, https://doi.org/10.1155/2010/805716.

    • Search Google Scholar
    • Export Citation
  • 28.

    Mack WJ, Preston-Martin S, Bernstein L, Qian D. Lifestyle and other risk factors for thyroid cancer in Los Angeles County females. Ann Epidemiol 2002; 12(6): 395401, https://doi.org/10.1016/S1047-2797(01)00281-2.

    • Search Google Scholar
    • Export Citation
  • 29.

    Mehta RG, Mehta RR. Vitamin D and cancer. J Nutr Biochem 2002; 13(5): 252264, https://doi.org/10.1016/S0955-2863(02)00183-3.

  • 30.

    Meng Li, Xinyu Liu, Na Liu, Tian Yang, Puyu Shi, Ruiqing He, . Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis. J Canc 2019; 10(16): 36393649, https://doi.org/10.7150/jca.33431.

    • Search Google Scholar
    • Export Citation
  • 31.

    Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215, https://doi.org/10.1093/nar/16.3.1215.

    • Search Google Scholar
    • Export Citation
  • 32.

    Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, . Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 2015; 69(3): 291296, https://doi.org/10.1038/ejcn.2014.265.

    • Search Google Scholar
    • Export Citation
  • 33.

    Ntais C, Polycarpou A, Ioannidis JP. Vitamin D receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Canc Epidemiol Biomarkers Prev 2003; 12(12): 13951402.

    • Search Google Scholar
    • Export Citation
  • 34.

    Oakley-Girvan I, Feldman D, Eccleshall TR, Gallagher RP, Wu AH, Kolonel LN, . Risk of early-onset prostate cancer in relation to germ line polymorphisms of the vitamin D receptor. Canc Epidemiol. Biomarkers Prev 2004; 13(8): 13251330.

    • Search Google Scholar
    • Export Citation
  • 35.

    Pan Z, Chen M, Hu X, Wang H, Yang J, Zhang C, . Associations between VDR gene polymorphisms and colorectal cancer susceptibility: an updated meta-analysis based on 39 case-control studies. Oncotarget 2018; 9(16): 1306813076, https://doi.org/10.18632/oncotarget.23964.

    • Search Google Scholar
    • Export Citation
  • 36.

    Peleg S, Abruzzese RV, Cooper CW, Gagel RF. Down-regulation of calcitonin gene transcription by vitamin D requires two widely separated enhancer sequences. Mol Endocrinol 1993; 7(8): 9991008, https://doi.org/10.1210/mend.7.8.8232320.

    • Search Google Scholar
    • Export Citation
  • 37.

    Penna-Martinez M, Ramos-Lopez E, Stern J, Hinsch N, Hansmann ML, Selkinski I, . Vitamin D receptor polymorphisms in differentiated thyroid carcinoma. Thyroid 2009; 19(6): 623628, https://doi.org/10.1089/thy.2008.0388.

    • Search Google Scholar
    • Export Citation
  • 38.

    Rao SN, Cabanillas ME. Navigating Systemic Therapy in Advanced Thyroid Carcinoma: From Standard of Care to Personalized Therapy and Beyond. J Endocr Soc 2018; 2(10): 11091130, https://doi.org/10.1210/js.2018-00180.

    • Search Google Scholar
    • Export Citation
  • 39.

    Rohan T. Epidemiological studies of vitamin D and breast cancer. Nutr Rev 2007; 65(8 Pt 2): S80S83, https://doi.org/nr.2007.aug.S80–S83.

    • Search Google Scholar
    • Export Citation
  • 40.

    Ron E, Kleinerman RA, Boice JD Jr., LiVolsi VA, Flannery JT, Fraumeni JF Jr. A population-based case-control study of thyroid cancer. J Natl Cancer Inst 1987; 79(1): 112, https://doi.org/10.1093/jnci/79.1.1.

    • Search Google Scholar
    • Export Citation
  • 41.

    Roskies M, Dolev Y, Caglar D, Hier MP, Mlynarek A, Majdan A, . Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer. J Otolaryngol Head Neck Surg 2012; 41: 160163.

    • Search Google Scholar
    • Export Citation
  • 42.

    Sahin M, Ucan B, Ginis Z, Topaloglu O, Gungunes A, Bozkurt NC, . Vitamin D3 levels and insulin resistance in papillary thyroid cancer patients. Med Oncol 2013; 30(2): 589, https://doi.org/10.1007/s12032-013-0589-5.

    • Search Google Scholar
    • Export Citation
  • 43.

    Shahabi A, Alipour M, Safiri H, Tavakol P, Alizadeh M, Milad Hashemi S, . Vitamin D receptor gene polymorphism: association with susceptibility to early-onset breast cancer in Iranian, BRCA1/2-mutation carrier and non-carrier patients. Pathol Oncol Res 2018; 24(3): 601607, https://doi.org/10.1007/s12253-017-0281-8.

    • Search Google Scholar
    • Export Citation
  • 44.

    Shahid MA, Sharma S. Physiology, Thyroid Hormone USA: StatPearls, Treasure Island (FL); 2019.

  • 45.

    Stepien T, Krupinski R, Sopinski J, Kuzdak K, Komorowski J, Lawnicka H, . Decreased 1–25 dihydroxyvitamin D3 concentration in peripheral blood serum of patients with thyroid cancer. Arch Med Res 2010; 41: 190194, https://doi.org/10.1016/j.arcmed.2010.04.004.

    • Search Google Scholar
    • Export Citation
  • 46.

    Vasilovici AF, Grigore LE, Ungureanu L, Fechete O, Candrea E, Trifa AP, . Vitamin D receptor polymorphisms and melanoma. Oncol Lett 2019; 17(5): 41624169, https://doi.org/10.3892/ol.2018.9733.

    • Search Google Scholar
    • Export Citation
  • 47.

    Wu S, Sun J. Vitamin D, vitamin D receptor, and macroautophagy in inflammation and infection. Discov Med 2011; 11(59): 325335.

  • 48.

    Zabel M, Dietel M. Calcitriol decreases calcitonin secretion from a human medullary carcinoma cell line via specific receptor action. Acta Endocrinol (Copenh) 1991; 125(3): 299304, https://doi.org/10.1530/acta.0.1250299.

    • Search Google Scholar
    • Export Citation
  • 49.

    Zabel M, Flig K, Gebarowska E, Surdyk-Zasada J. The effect of calcitriol and its analogues on proliferation and hormone expression in cultured cells of thyroid medullary carcinomas. Folia Morphol (Warsz) 2003; 62(4): 463465.

    • Search Google Scholar
    • Export Citation
  • 50.

    Zabel M, Gebarowska E, Drag-Zalesinska M, Wysocka T. Effect of calcitriol on proliferation of TT cells and on expression of calcitonin gene. Folia Histochem Cytobiol 2002; 40(2): 187188.

    • Search Google Scholar
    • Export Citation

The author instruction is available in PDF.

Please, download the file from HERE

  • Impact Factor (2018): 1.113
  • Physiology (medical) SJR Quartile Score (2018): Q4
  • Scimago Journal Rank (2018): 0.262
  • SJR Hirsch-Index (2018): 26

Language: English

Founded in 1950
Publication: One volume of four issues annually
Publication Programme: 2020. Vol. 107
Indexing and Abstracting Services:

  • Biological Abstracts
  • BIOSIS Previews
  • CAB Abstracts
  • EMBASE/Excerpta Medica
  • Global Health
  • Index Copernicus
  • Index Medicus
  • Medline
  • Referativnyi Zhurnal
  • SCOPUS
  • Social Science Citation Index

 

Subscribers can access the electronic version of every printed article.

Senior editors

Editor(s)-in-Chief: Rosivall, László

Managing Editor(s): Bartha, Jenő; Berhidi, Anna

Co-editor(s): Koller, Ákos; Lénárd, László; Szénási, Gábor; Radák, Zsolt

Assistant Editor(s): G. Dörnyei (Budapest), Zs. Miklós (Budapest), Gy. Nádasy (Budapest)

Hungarian Editorial Board

      Benedek, György (Szeged)
      Benyó, Zoltán (Budapest)
      Boros, Mihály (Szeged)
      Chernoch, László (Debrecen)
      Détári, László (Budapest)
      Hamar, János (Budapest)
      Hantos, Zoltán (Szeged)
      Hunyady, László (Budapest)
      Jancsó, Gábor (Szeged)
      Karádi, Zoltán (Pécs)
      Kovács, László (Debrecen)
      Palkovits, Miklós (Budapest)
      Papp, Gyula (Szeged)
      Pavlik, Gábor (Budapest)
      Spät, András (Budapest)
      Szabó, Gyula (Szeged)
      Szelényi, Zoltán (Pécs)
      Szollár, Lajos (Budapest)
      Szücs, Géza (Debrecen)
      Telegdy, Gyula (Szeged)
      Toldi, József (Szeged)
      Tósaki, Árpád (Debrecen)

 

International Editorial Board

      R. Bauer (Jena)
      W. Benjelloun (Rabat)
      A. W. Cowley Jr. (Milwaukee)
      D. Djuric (Belgrade)
      C. Fry (London)
      S. Greenwald (London)
      O. Hänninen (Kuopio)
      H. G. Hinghofer-Szalkay (Graz)
      Gy. Kunos (Richmond)
      M. Mahmoudian (Tehran)
      T. Mano (Seki, Gifu)
      G. Navar (New Orleans)
      H. Nishino (Nagoya)
      O. Petersen (Liverpool)
      U. Pohl (Münich)
      R. S. Reneman (Maastricht)
      A. Romanovsky (Phoenix)
      G. M. Rubanyi (Richmond)
      T. Sakata (Oita)
      A. Siddiqui (Karachi)
      Cs. Szabo (Beverly)
      E. Vicaut (Paris)
      N. Westerhof (Amsterdam)
      L. F. Zhang (Xi'an)

Editorial Office:
Akadémiai Kiadó Zrt.
Prielle Kornélia u. 21–35, H-1117 Budapest, Hungary

Editorial Correspondence:
Physiology International
Semmelweis University, Faculty of Medicine Institute of Pathophysiology
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: pi@semmelweis-univ.hu