Skip to main content

Advertisement

SpringerLink
Log in

Cigarette Smoking and hOGG1 Ser326Cys Polymorphism are Associated with 8-OHdG Accumulation on Mitochondrial DNA in Thoracic Esophageal Squamous Cell Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2′-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC).

Methods

DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing.

Results

Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0–20, 20–40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051).

Conclusions

Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–65.

    Article  PubMed  CAS  Google Scholar 

  2. Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol. 2005;37:822–34.

    Article  PubMed  CAS  Google Scholar 

  3. Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA. 1997;94:514–9.

    Article  PubMed  CAS  Google Scholar 

  4. Lee HC, Lu CY, Fahn HJ, et al. Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441:292–6.

    Article  PubMed  CAS  Google Scholar 

  5. Lee HC, Yin PH, Lu CY, et al. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000;348 Pt 2:425–32.

    Article  PubMed  CAS  Google Scholar 

  6. Kim MM, Clinger JD, Masayesva BG, et al. Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions. Clin Cancer Res. 2004;10:8512–5.

    Article  PubMed  CAS  Google Scholar 

  7. Poulsen HE. Oxidative DNA modifications. Exp Toxicol Pathol. 2005;57(1):161–9.

    Article  PubMed  CAS  Google Scholar 

  8. Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog. 2006;5:14.

    Article  PubMed  Google Scholar 

  9. Cheng KC, Cahill DS, Kasai H, et al. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G—T and A—C substitutions. J Biol Chem. 1992;267:166–72.

    PubMed  CAS  Google Scholar 

  10. Kasai H, Chung MH, Jones DS, et al. 8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis. J Toxicol Sci. 1991;16(1):95–105.

    Article  PubMed  CAS  Google Scholar 

  11. Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature. 1991; 349:431–4.

    Article  PubMed  CAS  Google Scholar 

  12. Boiteux S, Radicella JP. The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys. 2000;377:1–8.

    Article  PubMed  CAS  Google Scholar 

  13. Kohno T, Shinmura K, Tosaka M, et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16:3219–25.

    Article  PubMed  CAS  Google Scholar 

  14. Lin CS, Chang SC, Wei YH, et al. Prognostic variables in thoracic esophageal squamous cell carcinoma. Ann Thorac Surg. 2009;87:1056–65.

    Article  PubMed  Google Scholar 

  15. Lin CS, Chang SC, Wang LS, et al. The role of mitochondrial DNA alterations in esophageal squamous cell carcinomas. J Thorac Cardiovasc Surg. 2010;139:189–97 e184.

    Article  Google Scholar 

  16. Valavanidis A, Vlachogianni T, Fiotakis K. Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. Int J Environ Res Public Health. 2009;6:445–62.

    Article  PubMed  CAS  Google Scholar 

  17. Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer Staging Manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17:1721–4.

    Article  PubMed  Google Scholar 

  18. Lin CS, Wang LS, Tsai CM, et al. Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2008;7:954–8.

    Article  PubMed  Google Scholar 

  19. Sikorsky JA, Primerano DA, Fenger TW, et al. Effect of DNA damage on PCR amplification efficiency with the relative threshold cycle method. Biochem Biophys Res Commun. 2004;323:823–30.

    Article  PubMed  CAS  Google Scholar 

  20. Sugimura H, Kohno T, Wakai K, et al. hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 1999;8:669–74.

    PubMed  CAS  Google Scholar 

  21. Tarng DC, Tsai TJ, Chen WT, et al. Effect of human OGG1 1245C–>G gene polymorphism on 8-hydroxy-2′-deoxyguanosine levels of leukocyte DNA among patients undergoing chronic hemodialysis. J Am Soc Nephrol. 2001;12:2338–47.

    PubMed  CAS  Google Scholar 

  22. Chen SK, Hsieh WA, Tsai MH, et al. Age-associated decrease of oxidative repair enzymes, human 8-oxoguanine DNA glycosylases (hOgg1), in human aging. J Radiat Res (Tokyo). 2003;44:31–5.

    Article  CAS  Google Scholar 

  23. Le Marchand L, Donlon T, Lum-Jones A, et al. Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:409–12.

    PubMed  Google Scholar 

  24. Farinati F, Cardin R, Bortolami M, et al. Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism. Int J Cancer. 2008;123:51–5.

    Article  PubMed  CAS  Google Scholar 

  25. Miyake H, Hara I, Kamidono S, et al. Prognostic significance of oxidative DNA damage evaluated by 8-hydroxy-2′-deoxyguanosine in patients undergoing radical nephrectomy for renal cell carcinoma. Urology. 2004;64:1057–61.

    Article  PubMed  Google Scholar 

  26. Rasanen JV, Sihvo EI, Ahotupa MO, et al. The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours. Eur J Surg Oncol. 2007;33:1164–8.

    Article  PubMed  CAS  Google Scholar 

  27. Olliver JR, Hardie LJ, Dexter S, et al. DNA damage levels are raised in Barrett’s oesophageal mucosa relative to the squamous epithelium of the oesophagus. Biomarkers. 2003;8:509–21.

    Article  PubMed  CAS  Google Scholar 

  28. Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.

    Article  PubMed  CAS  Google Scholar 

  29. Wu IC, Lu CY, Kuo FC, et al. Interaction between cigarette, alcohol and betel nut use on esophageal cancer risk in Taiwan. Eur J Clin Invest. 2006;36:236–41.

    Article  PubMed  CAS  Google Scholar 

  30. Lu J, Sharma LK, Bai Y. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 2009;19:802–15.

    Article  PubMed  CAS  Google Scholar 

  31. Xing DY, Tan W, Song N, et al. Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer. 2001;95:140–3.

    Article  PubMed  CAS  Google Scholar 

  32. Kim JI, Park YJ, Kim KH, et al. hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol. 2003;9:956–60.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by Grants from the Department of Health, Executive Yuan, Taiwan (No. 97-04, 98-08, and 99-05) and National Science Council, Taiwan (NSC 100-2314-B-192-001).

Author information

Authors and Affiliations

  1. Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chen-Sung Lin MD, PhD & Wen-Hu Hsu MD

  2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Chen-Sung Lin MD, PhD, Liang-Shun Wang MD, Teh-Ying Chou MD, PhD, Shi-Chuan Chang MD, PhD & Yau-Huei Wei PhD

  3. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan

    Shi-Chuan Chang MD, PhD

  4. Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan

    Shu-Yu Lee MSc & Yau-Huei Wei PhD

  5. Mackay Medical College, New Taipei City, Taiwan

    Yau-Huei Wei PhD

  6. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan

    Liang-Shun Wang MD

  7. Leisure and Recreation Management, Kainan University, Taoyuan, Taiwan

    Hui-Chen Lin PhD

  8. Division of Thoracic Surgery, Department of Surgery, Taipei Hospital, Department of Health, Executive Yuan, New Taipei City, Taiwan

    Chen-Sung Lin MD, PhD & Shu-Yu Lee MSc

  9. Division of Gastroenterology, Department of Internal Medicine, Taipei Hospital, Department of Health, Executive Yuan, New Taipei City, Taiwan

    Mau-Hua Lee MD

  10. Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Wen-Hu Hsu MD

  11. Division of General Chest Medicine, Department of Chest, Taipei Veterans General Hospital, Taipei, Taiwan

    Shi-Chuan Chang MD, PhD

  12. Division of Surgical Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Teh-Ying Chou MD, PhD

  13. Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

    Liang-Shun Wang MD

Authors
  1. Chen-Sung Lin MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang-Shun Wang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teh-Ying Chou MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Hu Hsu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui-Chen Lin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shu-Yu Lee MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mau-Hua Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shi-Chuan Chang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yau-Huei Wei PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shi-Chuan Chang MD, PhD or Yau-Huei Wei PhD.

Additional information

S.-C. Chang and Y.-H. Wei contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, CS., Wang, LS., Chou, TY. et al. Cigarette Smoking and hOGG1 Ser326Cys Polymorphism are Associated with 8-OHdG Accumulation on Mitochondrial DNA in Thoracic Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 20 (Suppl 3), 379–388 (2013). https://doi.org/10.1245/s10434-012-2576-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-012-2576-z

Keywords

Search

Navigation