Skip to main content

Advertisement

Log in

Molecular profiling of papillary thyroid carcinomas in healthcare workers exposed to low dose radiation at the workplace

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Exposure to ionizing radiation, especially during childhood, is a well-established risk factor for thyroid cancer. The vast majority of radiation-induced cancers are papillary carcinomas (PTCs). These tumors typically have gene fusions in contrast to point mutations prevalent in sporadic PTCs. The aim of this study was to investigate the molecular profiles of PTC patients with workplace exposure to ionizing radiation.

Methods

A retrospective review of 543 patients who underwent surgery with diagnosis of PTC was performed. A cohort of nine healthcare specialists previously exposed to radiation sources during their professional practice was selected and analyzed using the ThyroSeq mutation panel for point mutations and gene fusions associated with thyroid cancer.

Results

The molecular analysis of surgical samples of PTCs was informative and revealed genetic alterations in five patients. BRAF V600E was found in four (67%) cases whereas RET/PTC1 fusion in one (17%) and one sample (17%) was wild type for point mutations and fusions. One sample completely failed molecular analysis while two others were negative for genes fusions but failed DNA analysis; these three samples were excluded.

Conclusions

In this limited cohort of healthcare workers exposed to low dose of ionizing radiation at the workplace and developed PTC, the molecular profiling determined BRAF V600E point mutation as the most common event, arguing against the role of workplace radiation exposure in the etiology of these tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this article.

References

  1. R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2019. CA Cancer J. Clin. 69(1), 7–34 (2019)

    Article  PubMed  Google Scholar 

  2. American Cancer Society, Cancer Facts & Figures 2019. (Atlanta, GA: American Cancer Society, 2019)

  3. V. Nose, Familial thyroid cancer: a review. Mod. Pathol. 24(Suppl 2), S19–S33 (2011)

    Article  CAS  PubMed  Google Scholar 

  4. C.M. Kitahara, J.A. Sosa, The changing incidence of thyroid cancer. Nat. Rev. Endocrinol. 12(11), 646–653 (2016)

    Article  PubMed  Google Scholar 

  5. J.A. Sipos, E.L. Mazzaferri, Thyroid cancer epidemiology and prognostic variables. Clin. Oncol. 22(6), 395–404 (2010)

    Article  CAS  Google Scholar 

  6. J. Ferlay et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136(5), E359–E386 (2015)

    Article  CAS  PubMed  Google Scholar 

  7. M.T. Islam, Radiation interactions with biological systems. Int. J. Radiat. Biol. 93(5), 487–493 (2017)

    Article  CAS  PubMed  Google Scholar 

  8. V.A. LiVolsi et al. The Chernobyl thyroid cancer experience: pathology. Clin. Oncol. 23(4), 261–267 (2011)

    Article  CAS  Google Scholar 

  9. M. Tronko et al. Radiation induced thyroid cancer: fundamental and applied aspects. Exp. Oncol. 32(3), 200–204 (2010)

    CAS  PubMed  Google Scholar 

  10. E.S. Gilbert, Ionising radiation and cancer risks: what have we learned from epidemiology? Int. J. Radiat. Biol. 85(6), 467–482 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Y. Nikiforov, D.R. Gnepp, Pediatric thyroid cancer after the Chernobyl disaster. Pathomorphologic study of 84 cases (1991-1992) from the Republic of Belarus. Cancer 74(2), 748–766 (1994)

    Article  CAS  PubMed  Google Scholar 

  12. B.J. Duffy Jr, P.J. Fitzgerald, Thyroid cancer in childhood and adolescence; a report on 28 cases. Cancer 3(6), 1018–1032 (1950)

    Article  PubMed  Google Scholar 

  13. E.L. Socolow et al. Thyroid carcinoma in man after exposure to ionizing radiation. A summary of the findings in Hiroshima and Nagasaki. N. Engl. J. Med. 268, 406–410 (1963)

    Article  CAS  PubMed  Google Scholar 

  14. J.W. Wood et al. Thyroid carcinoma in atomic bomb survivors Hiroshima and Nagasaki. Am. J. Epidemiol. 89(1), 4–14 (1969)

    Article  CAS  PubMed  Google Scholar 

  15. D.R. Hollingsworth, Radiation and carcinoma of the thyroid. Conn. Med. 27, 762–765 (1963)

    CAS  PubMed  Google Scholar 

  16. K. Takahashi et al. The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose. Mol. Carcinog. 46(3), 242–248 (2007)

    Article  CAS  PubMed  Google Scholar 

  17. K. Hamatani et al. RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose. Cancer Res. 68(17), 7176–7182 (2008)

    Article  CAS  PubMed  Google Scholar 

  18. E. Ron et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat. Res 141(3), 259–277 (1995)

    Article  CAS  PubMed  Google Scholar 

  19. L.H. Veiga et al. Thyroid cancer after childhood exposure to external radiation: an updated pooled analysis of 12 studies. Radiat. Res. 185(5), 473–484 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Y. Nikiforov, D.R. Gnepp, J.A. Fagin, Thyroid lesions in children and adolescents after the Chernobyl disaster: implications for the study of radiation tumorigenesis. J. Clin. Endocrinol. Metab. 81(1), 9–14 (1996)

    CAS  PubMed  Google Scholar 

  21. F. Pacini et al. Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France. J. Clin. Endocrinol. Metab. 82(11), 3563–3569 (1997)

    CAS  PubMed  Google Scholar 

  22. L.M. Morton et al. Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident. Sci 2021. 372(6543)

  23. E. Cardis et al. Risk of thyroid cancer after exposure to 131I in childhood. J. Natl Cancer Inst. 97(10), 724–732 (2005)

    Article  PubMed  Google Scholar 

  24. D. Williams, Cancer after nuclear fallout: lessons from the Chernobyl accident. Nat. Rev. Cancer 2(7), 543–549 (2002)

    Article  CAS  PubMed  Google Scholar 

  25. E.K. Cahoon et al. Risk of thyroid nodules in residents of belarus exposed to chernobyl fallout as children and adolescents. J. Clin. Endocrinol. Metab. 102(7), 2207–2217 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  26. A.B. Schneider et al. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid. J. Clin. Endocrinol. Metab. 77(2), 362–369 (1993)

    CAS  PubMed  Google Scholar 

  27. M.J. Adams et al. Thyroid cancer risk 40+ years after irradiation for an enlarged thymus: an update of the Hempelmann cohort. Radiat. Res. 174(6), 753–762 (2010)

    Article  CAS  PubMed  Google Scholar 

  28. Y.E. Nikiforov, Radiation-induced thyroid cancer: what we have learned from chernobyl. Endocr. Pathol. 17(4), 307–317 (2006)

    Article  CAS  PubMed  Google Scholar 

  29. Y.E. Nikiforov, Is ionizing radiation responsible for the increasing incidence of thyroid cancer? Cancer 116(7), 1626–1628 (2010)

    Article  PubMed  Google Scholar 

  30. Cancer Genome Atlas Research, N., Integrated genomic characterization of papillary thyroid carcinoma. Cell 159(3), 676–690 (2014)

    Article  Google Scholar 

  31. R.J. Leeman-Neill et al. RET/PTC and PAX8/PPARgamma chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics. Cancer 119(10), 1792–1799 (2013)

    Article  CAS  PubMed  Google Scholar 

  32. J.C. Ricarte-Filho et al. Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J. Clin. Invest. 123(11), 4935–4944 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. R. Ciampi et al. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest. 115(1), 94–101 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. A.A. Efanov et al. Investigation of the relationship between radiation dose and gene mutations and fusions in post-chernobyl thyroid cancer. J. Natl Cancer Inst. 110(4), 371–378 (2018)

    Article  CAS  PubMed  Google Scholar 

  35. R.J. Leeman-Neill et al. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer 120(6), 799–807 (2014)

    Article  CAS  PubMed  Google Scholar 

  36. V. Lope et al. Occupation and thyroid cancer risk in Sweden. J. Occup. Environ. Med. 47(9), 948–957 (2005)

    Article  PubMed  Google Scholar 

  37. E. Albi, et al., Radiation and thyroid cancer. Int J Mol. Sci. 18(5) (2017)

  38. J.X. Wang et al. Cancer incidence among medical diagnostic X-ray workers in China, 1950 to 1985. Int. J. Cancer 45(5), 889–895 (1990)

    Article  CAS  PubMed  Google Scholar 

  39. G. Wingren et al. Occupation and female papillary cancer of the thyroid. J. Occup. Environ. Med. 37(3), 294–297 (1995)

    Article  CAS  PubMed  Google Scholar 

  40. R, L., WHO classification of tumors of endocrine organs. 2017

  41. Y.E. Nikiforov et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer 120(23), 3627–3634 (2014)

    Article  CAS  PubMed  Google Scholar 

  42. Y.E. Nikiforov et al. Impact of the multi-gene thyroseq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid 25(11), 1217–1223 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. S. Leslie, G. Mary, W. Christian, TNM Classification of Malignant Tumors, 7th Edition. (New Jersey, 2011)

  44. M.L. Iglesias et al. Radiation exposure and thyroid cancer: a review. Arch. Endocrinol. Metab. 61(2), 180–187 (2017)

    Article  PubMed  Google Scholar 

  45. L.T. Dilas et al. [Iodine and thyroid gland with or without nuclear catastrophe]. Med. Pregl. 65(11–12), 489–495 (2012)

    PubMed  Google Scholar 

  46. Y.E. Nikiforov et al. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 57(9), 1690–1694 (1997)

    CAS  PubMed  Google Scholar 

  47. H.M. Rabes et al. Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications. Clin. Cancer Res. 6(3), 1093–1103 (2000)

    CAS  PubMed  Google Scholar 

  48. L. Fugazzola et al. Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. Cancer Res. 55(23), 5617–5620 (1995)

    CAS  PubMed  Google Scholar 

  49. M.N. Nikiforova et al. Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas. Cancer Lett. 209(1), 1–6 (2004)

    Article  CAS  PubMed  Google Scholar 

  50. L. Luis, S. Augusto, Digital Imaging System for Plain Radiography. (New York, Springer, 2013)

  51. S. Preston-Martin, B.E. Henderson, L. Bernstein, Medical and dental x rays as risk factors for recently diagnosed tumors of the head. Natl Cancer Inst. Monogr. 69, 175–179 (1985)

    CAS  PubMed  Google Scholar 

  52. S. Preston-Martin et al. Prior exposure to medical and dental X-rays related to tumors of the parotid gland. J. Natl Cancer Inst. 80(12), 943–949 (1988)

    Article  CAS  PubMed  Google Scholar 

  53. W.T. Longstreth Jr et al. Dental X-rays and the risk of intracranial meningioma: a population-based case-control study. Cancer 100(5), 1026–1034 (2004)

    Article  PubMed  Google Scholar 

  54. A. Memon et al. Dental X-rays and the risk of thyroid cancer and meningioma: a systematic review and meta-analysis of current epidemiological evidence. Thyroid 29(11), 1572–1593 (2019)

    Article  PubMed  Google Scholar 

  55. M.A. Han, J.H. Kim, Diagnostic X-ray exposure and thyroid cancer risk: systematic review and meta-analysis. Thyroid 28(2), 220–228 (2018)

    Article  PubMed  Google Scholar 

  56. A. Hallquist et al. Medical diagnostic and therapeutic ionizing radiation and the risk for thyroid cancer: a case-control study. Eur. J. Cancer Prev. 3(3), 259–267 (1994)

    Article  CAS  PubMed  Google Scholar 

  57. P.D. Inskip et al. Medical diagnostic x rays and thyroid cancer. J. Natl Cancer Inst. 87(21), 1613–1621 (1995)

    Article  CAS  PubMed  Google Scholar 

  58. A. Bounacer et al. High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation. Oncogene 15(11), 1263–1273 (1997)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Y.E.N. and C.S.D. designed and developed the study. A.V., J.C., F.J., J.P.D., M.A., helped with samples collection. V.C. carried out the experiments, data analysis, and wrote the article with support from Y.E.N. and M.N.N. All authors participated in the revision of the manuscript.

Corresponding author

Correspondence to Vincenzo Condello.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Informed consent was obtained from all individual participants included in the study.

Ethical approval

The study was performed in accordance with the Declaration of Helsinki and its later amendments, and it was approved by the Institutional Review Board from both Hospital Pablo Tobón Uribe and Clínica las Americas, in Medellin, Colombia.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duque, C.S., Vélez, A., Cuartas, J. et al. Molecular profiling of papillary thyroid carcinomas in healthcare workers exposed to low dose radiation at the workplace. Endocrine 76, 95–100 (2022). https://doi.org/10.1007/s12020-021-02972-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02972-y

Keywords

Navigation