Genetic markers associated with resistance to radioiodine therapy in thyroid cancer patients: Prospective cohort study

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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.

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; Moscow

Grigorij 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, Moscow

Reis H. Mukhamadiev

Russian Medical Academy of Continuous Professional Education

Email: rmuhamadiev@gmail.com
ORCID iD: 0000-0002-8052-4984

Resident

Russian Federation, Moscow

Oksana M. Perfilieva

Russian Medical Academy of Continuous Professional Education

Email: operfileva@mail.ru
SPIN-code: 5453-5031

Cand. Sci. (Med.)

Russian Federation, Moscow

Ruslan 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, Moscow

Anastasia 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, Moscow

Olga I. Milyutina

Russian Medical Academy of Continuous Professional Education

Email: miliutina.olia2017@yandex.ru
ORCID iD: 0000-0002-6828-3831

Resident

Russian Federation, Moscow

Olga V. Konenkova

Russian Medical Academy of Continuous Professional Education

Email: konenkova.olia@yandex.ru
ORCID iD: 0000-0002-4789-2718

Resident

Russian Federation, Moscow

Sergey 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, Moscow

Dmitriy 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; Moscow

Irina 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; Moscow

Sergey L. Kirienko

Russian Medical Academy of Continuous Professional Education

Email: ii_po_klinica_rmapo@mail.ru

Department Рead

Russian Federation, Moscow

Elena M. Zhmaeva

Russian Medical Academy of Continuous Professional Education

Email: zhem1504@mail.ru

Cand. Sci. (Med.)

Russian Federation, Moscow

Karin 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; Moscow

Alexander 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, Moscow

Irina 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, Moscow

Dmitry 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, Moscow

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