Genetic markers associated with resistance to radioiodine therapy in thyroid cancer patients: Prospective cohort study
- Authors: Denisenko N.P.1,2, Shuev G.N.2, Mukhamadiev R.H.2, Perfilieva O.M.2, Kazakov R.E.2, Kachanova A.A.2, Milyutina O.I.2, Konenkova O.V.2, Ryzhkin S.A.2, Ivashchenko D.V.1,2, Bure I.V.1,2, Kirienko S.L.2, Zhmaeva E.M.2, Mirzaev K.B.1,2, Ametov A.S.2, Poddubnaya I.V.2, Sychev D.A.2
-
Affiliations:
- Centre for Personalized Medicine
- Russian Medical Academy of Continuous Professional Education
- Issue: Vol 24, No 3 (2022)
- Pages: 345-350
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/110799
- DOI: https://doi.org/10.26442/18151434.2022.3.201867
- ID: 110799
Cite item
Full Text
Abstract
Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients.
Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients.
Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.5±15.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan™ kits.
Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p>0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04.
Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Natalia P. Denisenko
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: natalypilipenko3990@gmail.com
ORCID iD: 0000-0003-3278-5941
SPIN-code: 5883-6249
Cand. Sci. (Med.)
Russian Federation, Saint Petersburg; MoscowGrigorij N. Shuev
Russian Medical Academy of Continuous Professional Education
Email: shuevgrigorii@gmail.com
ORCID iD: 0000-0002-5031-0088
SPIN-code: 4172-1330
Res. Assist.
Russian Federation, MoscowReis H. Mukhamadiev
Russian Medical Academy of Continuous Professional Education
Email: rmuhamadiev@gmail.com
ORCID iD: 0000-0002-8052-4984
Resident
Russian Federation, MoscowOksana M. Perfilieva
Russian Medical Academy of Continuous Professional Education
Email: operfileva@mail.ru
SPIN-code: 5453-5031
Cand. Sci. (Med.)
Russian Federation, MoscowRuslan E. Kazakov
Russian Medical Academy of Continuous Professional Education
Email: rustic100@rambler.ru
ORCID iD: 0000-0003-0802-4229
SPIN-code: 8751-5090
Cand. Sci. (Biol.)
Russian Federation, MoscowAnastasia A. Kachanova
Russian Medical Academy of Continuous Professional Education
Email: aakachanova@yandex.ru
ORCID iD: 0000-0003-3194-4410
SPIN-code: 1214-8156
Res. Assist.
Russian Federation, MoscowOlga I. Milyutina
Russian Medical Academy of Continuous Professional Education
Email: miliutina.olia2017@yandex.ru
ORCID iD: 0000-0002-6828-3831
Resident
Russian Federation, MoscowOlga V. Konenkova
Russian Medical Academy of Continuous Professional Education
Email: konenkova.olia@yandex.ru
ORCID iD: 0000-0002-4789-2718
Resident
Russian Federation, MoscowSergey A. Ryzhkin
Russian Medical Academy of Continuous Professional Education
Email: rsa777@inbox.ru
ORCID iD: 0000-0003-2595-353X
SPIN-code: 5955-5712
D. Sci. (Med.), Assoc. Prof.
Russian Federation, MoscowDmitriy V. Ivashchenko
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: dvi1991@yandex.ru
ORCID iD: 0000-0002-2295-7167
SPIN-code: 9435-7794
D. Sci. (Med.)
Russian Federation, Saint Petersburg; MoscowIrina V. Bure
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: bureira@mail.ru
ORCID iD: 0000-0003-2043-5848
SPIN-code: 3212-7905
Cand. Sci. (Biol.)
Russian Federation, Saint Petersburg; MoscowSergey L. Kirienko
Russian Medical Academy of Continuous Professional Education
Email: ii_po_klinica_rmapo@mail.ru
Department Рead
Russian Federation, MoscowElena M. Zhmaeva
Russian Medical Academy of Continuous Professional Education
Email: zhem1504@mail.ru
Cand. Sci. (Med.)
Russian Federation, MoscowKarin B. Mirzaev
Centre for Personalized Medicine; Russian Medical Academy of Continuous Professional Education
Email: karin05doc@yandex.ru
ORCID iD: 0000-0002-9307-4994
SPIN-code: 8308-7599
D. Sci. (Med.)
Russian Federation, Saint Petersburg; MoscowAlexander S. Ametov
Russian Medical Academy of Continuous Professional Education
Email: alexander.ametov@gmail.com
ORCID iD: 0000-0002-7936-7619
SPIN-code: 9511-1413
D. Sci. (Med.), Prof.
Russian Federation, MoscowIrina V. Poddubnaya
Russian Medical Academy of Continuous Professional Education
Email: poddubnaya_irina@inbox.ru
ORCID iD: 0000-0002-0995-1801
SPIN-code: 1146-9889
D. Sci. (Med.), Prof., Acad. RAS
Russian Federation, MoscowDmitry A. Sychev
Russian Medical Academy of Continuous Professional Education
Email: dmitry.alex.sychev@gmail.com
ORCID iD: 0000-0002-4496-3680
SPIN-code: 4525-7556
D. Sci. (Med.), Prof., Acad. RAS
Russian Federation, MoscowReferences
- Van Nostrand D. The Benefits and Risks of I-131 Therapy in Patients with Well-Differentiated Thyroid Cancer. Thyroid. 2009;19(12):1381-91. doi: 10.1089/thy.2009.1611
- Клинические рекомендации «Дифференцированный рак щитовидной железы» (утв. Минздравом России, 2020 г.). Режим доступа: https://cr.minzdrav.gov.ru/recomend/329_1. Ссылка активна на 16.04.2022 [Clinical recommendations: differentiated thyroid cancer (approved by the Ministry of Health of Russia, 2020). Available at: https://cr.minzdrav.gov.ru/recomend/329_1. Accessed: 16.04.2022 (in Russian)].
- Jackson S, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071-8. doi: 10.1038/nature08467
- Yan M, Tang C, Ma Z, et al. DNA damage response in nephrotoxic and ischemic kidney injury. Toxicol Appl Pharmacol. 2016;313:104-108. doi: 10.1016/j.taap.2016.10.022
- Marechal A, Zou L. DNA Damage Sensing by the ATM and ATR Kinases. Cold Spring Harb Perspect Biol. 2013;5(9):a012716. doi: 10.1101/cshperspect.a012716
- Thomasova D, Mulay SR, Bruns H, Anders HJ. p53-Independent Roles of MDM2 in NF-κB Signaling: Implications for Cancer Therapy, Wound Healing, and Autoimmune Diseases. Neoplasia. 2012;14(12):1097-101. doi: 10.1593/neo.121534
- Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nat Cell Biol. 2013;15(7):713-20. doi: 10.1038/ncb2788
- Katayama M, Kawaguchi T, Berger M, Pieper R. DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ. 2007;14(3):548-58. doi: 10.1038/sj.cdd.4402030
- Dyavaiah M, Rooney J, Chittur S, et al. Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1. Mol Cancer Res. 2011;9(4):462-75. doi: 10.1158/1541-7786.mcr-10-0473
- Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27-42.
- Sridhar S, Botbol Y, Macian F, Cuervo A. Autophagy and disease: always two sides to a problem. J Pathol. 2011;226(2):255-73. doi: 10.1002/path.3025
- Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333(1-2):169-74. doi: 10.1016/0014-5793(93)80398-e
- Lamb C, Yoshimori T, Tooze S. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14(12):759-74. doi: 10.1038/nrm3696
- Ishibashi K, Fujita N, Kanno E, et al. Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12–5-16L2 complex. Autophagy. 2011;7(12):1500-13. doi: 10.4161/auto.7.12.18025
- Tang J, Wang D, Shen Y, Xue F. ATG16L2 overexpression is associated with a good prognosis in colorectal cancer. J Gastrointest Oncol. 2021;12(5):2192-202. doi: 10.21037/jgo-21-495
- Zhou Q, Chen X, Chen Q, et al. A Four Autophagy-Related Gene-Based Prognostic Signature for Pancreatic Cancer. Crit Rev Eukaryot Gene Expr. 2021;31(4):89-100. doi: 10.1615/critreveukaryotgeneexpr.2021038733
- Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1856-83. doi: 10.1093/annonc/mdz400
- Kastan MB, Lim DS, Kim ST, Yang D. ATM--A Key Determinant of Multiple Cellular Responses to Irradiation. Acta Oncol. (Madr). 2001;40(6):686-8. doi: 10.1080/02841860152619089
- Hickson I, Zhao Y, Richardson CJ, et al. Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM. Cancer Res. 2004;64(24):9152-9. doi: 10.1158/0008-5472.CAN-04-2727
- Aggarwal BB, Sung B. NF-κB in Cancer: A Matter of Life and Death: Figure 1. Cancer Discov. 2011;1(6):469-71. doi: 10.1158/2159-8290.CD-11-0260
- Perkins ND. The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer. 2012;12(2):121-32. doi: 10.1038/nrc3204
- Wu Z, Shi Y, Tibbetts R, Miyamoto S. Molecular Linkage Between the Kinase ATM and NF-κB Signaling in Response to Genotoxic Stimuli. Science. 2006;311(5764):1141-6. doi: 10.1126/science.1121513
- Plantinga T, Petrulea M, Oosting M, et al. Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma. Endocr Relat Cancer. 2017:307-18. doi: 10.1530/erc-17-0033
- Liu J, Tang X, Shi F, et al. Genetic polymorphism contributes to 131I radiotherapy-induced toxicities in patients with differentiated thyroid cancer. Pharmacogenomics. 2018;19(17):1335-44. doi: 10.2217/pgs-2018-0070
- Xie K, Liang C, Li Q, et al. Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival. Int J Cancer. 2016;139(7):1564-73. doi: 10.1002/ijc.30205
- Bai H, He Y, Lin Y, et al. Identification of a novel differentially methylated region adjacent to ATG16L2 in lung cancer cells using methyl-CpG binding domain protein-enriched genome sequencing. Genome. 2021;64(5):533-46. doi: 10.1139/gen-2020-0071
- Yang Z, Liu Z. Potentially functional variants of autophagy-related genes are associated with the efficacy and toxicity of radiotherapy in patients with nasopharyngeal carcinoma. Mol Genet Genomic Med. 2019;7(12):e1030. doi: 10.1002/mgg3.1030