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The OGG1 Ser326Cys polymorphism and its association with DNA damage and DNA repair in papillary thyroid cancer

Year 2025, Volume: 30 Issue: 1, 1 - 8, 29.01.2025
https://doi.org/10.21673/anadoluklin.1508336

Abstract

Aim: Hydrogen peroxide, locally produced during thyroid hormone synthesis, leads to oxidative stress in the thyroid gland. Defective repair of oxidative DNA lesions contributes to tumor development. This study aimed to understand the importance of DNA damage and repair on thyroid cancer development through the impact of the DNA repair gene OGG1 Ser326Cys polymorphism that has clinical significance in untreated patients with papillary thyroid cancer.

Methods: The study was performed with 70 patients with papillary thyroid cancer and 73 volunteers as control. In lymphocytes, endogenous DNA damage, H2O2-induced DNA damage, and DNA damage after repair were determined by comet assay. The polymerase chain reaction-restriction fragment length polymorphism method was performed for OGG1 genotyping.

Results: Endogenous DNA damage, H2O2-induced DNA damage, and DNA damage after repair were higher in patients with thyroid cancer than in the controls (P<0.001). An association was determined between the OGG1 Cys326 allele and increased risk for the development of papillary thyroid cancer. No significant difference was determined between cases carrying different OGG1 genotypes for endogenous DNA damage, H2O2-induced DNA damage, and DNA damage after repair in the study groups.

Conclusions: Endogenous DNA damage and cell susceptibility to oxidation increase, and DNA repair is impaired in patients with papillary thyroid cancer. However, the OGG1 Ser326Cys polymorphism is not responsible for the DNA repair defect.

Ethical Statement

The Cerrahpasa Medical Faculty Ethics Committee approved the study under the Declaration of Helsinki principles.

Supporting Institution

This study was supported and funded by Istanbul University Scientific Research Projects Unit. (Project No: 31271).

Project Number

Project No: 31271

References

  • Kroll TG, Sarraf P, Pecciarini L, Mueller E, Spiegelman BM, Fletcher JA. PAX8-PPAR gamma1 fusion oncogene in human thyroid carcinoma (corrected). Science. 2000; 289(5483):1357-60.
  • Fagin JA. Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol Endocrinol. 2002; 16(5):903-11
  • De Deken X, Wang D, Dumont JE, Miot F. Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. Exp Cell Res. 2002;273(2):187-96.
  • Krohn K, Maier J, Paschke R. Mechanisms of Disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nat Clin Pract Endocrinol Metab. 2007;3(10):713–20.
  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003;17(10):1195-214.
  • Kiwerska K, Szyfter K. DNA repair in cancer initiation, progression, and therapy-a double-edged sword. J Appl Genet. 2019;60(3-4):329-334.
  • Javid M, Sasanakietkul T, Nicolson NG, et al. DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers World J Surg. 2018;42(2):358-66.
  • Bruner SD, Norman DP, Verdine GL. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 2000;403(6272):859-66.
  • Kershaw RM, Hodges NJ. Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1. Mutagenesis. 2012;27(4):501-10.
  • Strober W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol. 2001; Appendix 3:Appendix 3B.
  • Dincer Y, Kankaya S. Comet Assay for Determining of DNA Damage: Review. Türkiye Klin J Med Sci. 2010;30:1365-73.
  • Sugimura H, Kohno T, Wakai K, et al. hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomark Prev. 1999;8(8):669-74.
  • Janik J, Czarnocka B. Oxidative DNA damage and repair in thyroid gland. Borgis-Postępy Nauk Medycznych 2011;24:950-6.
  • Stone JR, Yang. Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal. 2006;8(3-4):243-70.
  • Maier J, van Steeg H, van Oostrom C, Karger S, Paschke R, Krohn K. Deoxyribonucleic acid damage and spontaneous mutagenesis in the thyroid gland of rats and mice. Endocrinology 2006;147(7): 3391-7.
  • Karger S, Krause K, Engelhardt C, et al. Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours. J Mol Endocrinol. 2012;48(3):193–02.
  • Aka P, Mateuca R, Buchet JP, Thierens H, Kirsch-Volders M. Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations? Mutat Res. 2004;556(1-2):169-81.
  • Rohr P, da Silva J, Erdtmann B, et al. BER gene polymorphisms (OGG1 Ser326Cys and XRCC1 Arg194Trp) and modulation of DNA damage due to pesticides exposure. Environ Mol Mutagen. 2011;52(1):20-7.
  • Mateuca R, Aka PV, De Boeck M, Hauspie R, Kirsch-Volders M, Lison D. Influence of hOGG1, XRCC1 and XRCC3 genotypes on biomarkers of genotoxicity in workers exposed to cobalt or hard metal dusts. Toxicol Lett. 2005;156(2): 277-88.
  • Janik J, Swoboda M, Janowska B, et al. 8-Oxoguanine incision activity is impaired in lung tissues of NSCLC patients with the polymorphism of OGG1 and XRCC1 genes. Mutat Res. 2011;709-710: 21-31.
  • Takezaki T, Gao CM, Wu JZ, et al. hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. Int J Cancer. 2002;99(4):624-7.
  • Chen L, Elahi A, Pow-Sang J, Lazarus P, Park J. Association between polymorphism of human oxoguanine glycosylase 1 and risk of prostate cancer. J Urol. 2003;170(6 Pt 1):2471-4.
  • Cho EY, Hildesheim A, Chen CJ, et al. Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1. Cancer Epidemiol Biomarkers Prev. 2003;12(10):1100-4.
  • Xing DY, Tan W, Song N. Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer. 2001;95(3):140-3.
  • Niwa Y, Matsuo K, Ito H, Hirose K, Tajima K, Nakanishi T, et al. Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects. Gynecol Oncol. 2005;99(1):43-9.
  • García-Quispesa WA, Pérez-Machadoa G, Akdia A, et al. Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer. Mutat Res. 2011;709-710:67-72.
  • Santos LS, Branco SC, Silva SN, et al. Polymorphisms in base excision repair genes and thyroid cancer risk. Oncol Rep. 2012;28(5):1859-68.
  • García-Quispes WA, Pastor S, Galofré P, et al. Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patient. Mutat Res. 2013;750(1-2):34-9.
  • Altieri F, Grillo C, Maceroni M, Chichiarelli S. DNA damage and repair: from molecular mechanisms to health implications. Antiox Redox Signal. 2008;10(5):891-937.
  • Iarmarcovai G, Bonassi S, Botta A, Baan RA, Orsière T. Genetic polymorphisms and micronucleus formation: a review of the literature. Mutat Res. 2008;658(3):215-33.

OGG1 Ser326Cys polimorfizmi ve papiller tiroid kanserindeki DNA hasarı ve DNA onarımı ile ilişkisi

Year 2025, Volume: 30 Issue: 1, 1 - 8, 29.01.2025
https://doi.org/10.21673/anadoluklin.1508336

Abstract

Amaç: Tiroit hormonu sentezi sırasında lokal olarak üretilen hidrojen peroksit, tiroit bezinde oksidatif strese yol açmaktadır. Oksidatif DNA lezyonlarının kusurlu onarımı tümör gelişimine katkıda bulunur. Bu çalışmada, tedavi edilmemiş papiller tiroit kanserli hastalarda, DNA hasarı ve DNA onarımının tiroit kanseri gelişimindeki rolünün, klinik önemi olan DNA onarım geni OGG1 Ser326Cys polimorfizminin üzerinden belirlenmesi amaçlandı.

Yöntem: Çalışma papiller tiroit kanserli 70 hasta ve kontrol grubu olarak 73 gönüllü ile gerçekleştirildi. Lenfositlerde endojen DNA hasarı, H2O2 ile indüklenmiş DNA hasarı ve onarım sonrası DNA hasarı Comet yöntemi ile belirlendi. OGG1 genotiplemesi için polimeraz zincir reaksiyonu-kısıtlama fragman uzunluğu polimorfizmi yöntemi uygulandı.

Bulgular: Tiroit kanserli hastalarda endojen DNA hasarı, H2O2 ile indüklenmiş DNA hasarı ve onarım sonrası DNA hasarı kontrollere göre daha yüksekti (P<0.001). OGG1 Cys326 aleli ile papiller tiroit kanseri gelişme riskinin artması arasında bir ilişki belirlendi. Çalışma gruplarında farklı OGG1 genotipi taşıyan olgular arasında endojen DNA hasarı, H2O2 ile indüklenmiş DNA hasarı ve onarım sonrası DNA hasarı açısından anlamlı bir fark saptanmadı.

Sonuç: Papiller tiroit kanserli hastalarda endojen DNA hasarı ve hücrenin oksidasyona duyarlılığı artmakta, DNA onarımı bozulmaktadır. Ancak OGG1 Ser326Cys polimorfizmi DNA onarım defektinden sorumlu olmadığı gösterilmiştir.

Ethical Statement

Cerrahpaşa Tıp Fakültesi Etik Kurulu, çalışmayı Helsinki Bildirgesi ilkeleri çerçevesinde onayladı.

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeler Birimi tarafından desteklenmiştir. (Proje no: 31271)

Project Number

Project No: 31271

References

  • Kroll TG, Sarraf P, Pecciarini L, Mueller E, Spiegelman BM, Fletcher JA. PAX8-PPAR gamma1 fusion oncogene in human thyroid carcinoma (corrected). Science. 2000; 289(5483):1357-60.
  • Fagin JA. Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol Endocrinol. 2002; 16(5):903-11
  • De Deken X, Wang D, Dumont JE, Miot F. Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. Exp Cell Res. 2002;273(2):187-96.
  • Krohn K, Maier J, Paschke R. Mechanisms of Disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nat Clin Pract Endocrinol Metab. 2007;3(10):713–20.
  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003;17(10):1195-214.
  • Kiwerska K, Szyfter K. DNA repair in cancer initiation, progression, and therapy-a double-edged sword. J Appl Genet. 2019;60(3-4):329-334.
  • Javid M, Sasanakietkul T, Nicolson NG, et al. DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers World J Surg. 2018;42(2):358-66.
  • Bruner SD, Norman DP, Verdine GL. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 2000;403(6272):859-66.
  • Kershaw RM, Hodges NJ. Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1. Mutagenesis. 2012;27(4):501-10.
  • Strober W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol. 2001; Appendix 3:Appendix 3B.
  • Dincer Y, Kankaya S. Comet Assay for Determining of DNA Damage: Review. Türkiye Klin J Med Sci. 2010;30:1365-73.
  • Sugimura H, Kohno T, Wakai K, et al. hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomark Prev. 1999;8(8):669-74.
  • Janik J, Czarnocka B. Oxidative DNA damage and repair in thyroid gland. Borgis-Postępy Nauk Medycznych 2011;24:950-6.
  • Stone JR, Yang. Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal. 2006;8(3-4):243-70.
  • Maier J, van Steeg H, van Oostrom C, Karger S, Paschke R, Krohn K. Deoxyribonucleic acid damage and spontaneous mutagenesis in the thyroid gland of rats and mice. Endocrinology 2006;147(7): 3391-7.
  • Karger S, Krause K, Engelhardt C, et al. Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours. J Mol Endocrinol. 2012;48(3):193–02.
  • Aka P, Mateuca R, Buchet JP, Thierens H, Kirsch-Volders M. Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations? Mutat Res. 2004;556(1-2):169-81.
  • Rohr P, da Silva J, Erdtmann B, et al. BER gene polymorphisms (OGG1 Ser326Cys and XRCC1 Arg194Trp) and modulation of DNA damage due to pesticides exposure. Environ Mol Mutagen. 2011;52(1):20-7.
  • Mateuca R, Aka PV, De Boeck M, Hauspie R, Kirsch-Volders M, Lison D. Influence of hOGG1, XRCC1 and XRCC3 genotypes on biomarkers of genotoxicity in workers exposed to cobalt or hard metal dusts. Toxicol Lett. 2005;156(2): 277-88.
  • Janik J, Swoboda M, Janowska B, et al. 8-Oxoguanine incision activity is impaired in lung tissues of NSCLC patients with the polymorphism of OGG1 and XRCC1 genes. Mutat Res. 2011;709-710: 21-31.
  • Takezaki T, Gao CM, Wu JZ, et al. hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. Int J Cancer. 2002;99(4):624-7.
  • Chen L, Elahi A, Pow-Sang J, Lazarus P, Park J. Association between polymorphism of human oxoguanine glycosylase 1 and risk of prostate cancer. J Urol. 2003;170(6 Pt 1):2471-4.
  • Cho EY, Hildesheim A, Chen CJ, et al. Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1. Cancer Epidemiol Biomarkers Prev. 2003;12(10):1100-4.
  • Xing DY, Tan W, Song N. Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer. 2001;95(3):140-3.
  • Niwa Y, Matsuo K, Ito H, Hirose K, Tajima K, Nakanishi T, et al. Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects. Gynecol Oncol. 2005;99(1):43-9.
  • García-Quispesa WA, Pérez-Machadoa G, Akdia A, et al. Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer. Mutat Res. 2011;709-710:67-72.
  • Santos LS, Branco SC, Silva SN, et al. Polymorphisms in base excision repair genes and thyroid cancer risk. Oncol Rep. 2012;28(5):1859-68.
  • García-Quispes WA, Pastor S, Galofré P, et al. Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patient. Mutat Res. 2013;750(1-2):34-9.
  • Altieri F, Grillo C, Maceroni M, Chichiarelli S. DNA damage and repair: from molecular mechanisms to health implications. Antiox Redox Signal. 2008;10(5):891-937.
  • Iarmarcovai G, Bonassi S, Botta A, Baan RA, Orsière T. Genetic polymorphisms and micronucleus formation: a review of the literature. Mutat Res. 2008;658(3):215-33.
There are 30 citations in total.

Details

Primary Language English
Subjects Endocrinology, Clinical Chemistry, Clinical Sciences (Other)
Journal Section ORIGINAL ARTICLE
Authors

Çağlayan Akkaya Engin 0000-0002-1905-0775

Hakan Yavuzer 0000-0003-2685-6555

Serkan Teksöz 0000-0002-6733-5644

Selen Soylu 0000-0002-1459-399X

Meltem Mete 0000-0002-9297-8254

Serap Yavuzer 0000-0001-7618-9987

Ali Ata Tuz 0000-0002-9802-2317

Mehmet Güven 0000-0002-8749-1708

Yıldız Dincer 0000-0002-8393-7901

Project Number Project No: 31271
Publication Date January 29, 2025
Submission Date July 23, 2024
Acceptance Date October 18, 2024
Published in Issue Year 2025 Volume: 30 Issue: 1

Cite

Vancouver Akkaya Engin Ç, Yavuzer H, Teksöz S, Soylu S, Mete M, Yavuzer S, Tuz AA, Güven M, Dincer Y. The OGG1 Ser326Cys polymorphism and its association with DNA damage and DNA repair in papillary thyroid cancer. Anatolian Clin. 2025;30(1):1-8.

13151 This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.