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Factors Related to Serum Vitamin C Level in Terminally Ill Cancer Patients

말기암환자에서 혈청 비타민 C 농도와 연관된 인자들

  • Kim, Hyung Jun (Department of Family Medicine, Gachon University Gil Medical Center) ;
  • Hwang, In Cheol (Department of Family Medicine, Gachon University Gil Medical Center) ;
  • Yeom, Chang Hwan (Ucell Clinic) ;
  • Ahn, Hong Yup (Department of Statistics, Dongguk University) ;
  • Choi, Youn Seon (Department of Family Medicine, Korea University Guro Hospital) ;
  • Lee, Jae Jun (Department of Family Medicine, Gachon University Gil Medical Center) ;
  • Lim, Su Hyuk (Department of Family Medicine, Gachon University Gil Medical Center)
  • 김형준 (가천대학교 길병원 가정의학과) ;
  • 황인철 (가천대학교 길병원 가정의학과) ;
  • 염창환 (유셀의원) ;
  • 안홍엽 (동국대학교 통계학과) ;
  • 최윤선 (고려대학교 구로병원 가정의학과) ;
  • 이재준 (가천대학교 길병원 가정의학과) ;
  • 임수혁 (가천대학교 길병원 가정의학과)
  • Received : 2014.08.04
  • Accepted : 2014.10.23
  • Published : 2014.12.01

Abstract

Purpose: Serum vitamin C is one of the indicators for antioxidant levels in the body and it is lower in cancer patients compared with the healthy population. However, there have been few studies on the levels of serum vitamin C in terminally ill cancer patients and related factors. Methods: We followed 65 terminal cancer patients who were hospitalized in two palliative care units. We collected data of age, sex, cancer type, functional status, clinical symptoms, history of cancer therapy, and various laboratory findings including serum vitamin C level. Patients were categorized into two groups according to the quartile of serum vitamin C level (Q1-3 vs. Q4), which were compared each other. Stepwise multiple logistic regression analysis was used to identify factors related to serum vitamin C levels. Results: The mean serum vitamin C level was $0.44{\mu}g/mL$, and all patients fell into the category of vitamin C deficiency. Univariate analysis showed that The serum vitamin C level was lower in non-lung cancer patients (P=0.041) and febrile patients (P=0.034). Multivariate analysis adjusted for potential confounders such as lung cancer, fever, dysphagia, dyspnea, C reactive protein, and history of chemotherapy demonstrated that odds for low serum vitamin C level was 3.7 for patients receiving chemotherapy (P=0.046) and 7.22 for febrile patients (P=0.02). Conclusion: Vitamin C deficiency was very severe in terminally ill cancer patients, and it was associated with history of chemotherapy and fever.

목적: 혈청 비타민 C 수치는 체내 항산화상태를 나타내는 지표로서, 암환자에서는 정상인에 비해 감소되어 있다. 하지만, 이 지표가 말기암환자에서 어느 정도 감소되어 있고, 그 감소에 어떤 요인들이 관련되는지에 대한 연구는 매우 드물다. 방법: 두 개 기관의 완화의료병동에 입원했던 암환자 65명을 대상으로 하였다. 환자의 나이, 성별, 암의 종류, 기능상태, 임상증상, 완치 목적의 암 치료력, 그리고 혈청 비타민 C를 포함한 혈액검사 자료를 수집하였다. 혈청 비타민 C 수치의 사분위수를 기준으로 두 군(3사분위수 이하 vs. 4 사분위수)으로 분류한 후 각 군의 차이를 비교하였고, 단계적 다중 로지스틱 회귀분석을 통해 혈청 비타민 C 수치와 관련된 인자를 확인하였다. 결과: 대상자의 혈청 비타민 C의 평균은 $0.44{\mu}g/mL$이었으며, 대상자 전체가 비타민 C 결핍에 해당되었다. 단변량 분석에서는, 비폐암 환자이거나(P=0.041) 발열이 있는 환자(P=0.034)에서 낮은 혈청 비타민 C 수치를 보였다. 폐암, 발열, 삼킴곤란, 호흡곤란, C 반응단백, 그리고 항암화학요법 등의 잠재적인 인자들을 보정한 다변량 분석에서, 낮은 혈청 비타민 C 수치를 나타낼 가능성은 항암화학요법을 받은 군에서 그렇지 않은 군에 비해 3.7배 높았고(P=0.046), 발열이 있는 군에서 그렇지 않은 군에 비해 7.22배 높았다(P=0.020). 결론: 말기암환자에서 비타민 C 부족은 매우 심각하였고, 항암화학요법 치료력과 발열이 관련 있었다.

Keywords

References

  1. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev 1997;23:209-40. https://doi.org/10.1016/S0305-7372(97)90012-8
  2. Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol 1999;35:273-7. https://doi.org/10.1016/S1368-8375(98)00115-8
  3. Yeh CC, Hou MF, Tsai SM, Lin SK, Hsiao JK, Huang JC, et al. Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clin Chim Acta 2005; 361:104-11. https://doi.org/10.1016/j.cccn.2005.05.002
  4. Pathak SK, Sharma RA, Steward WP, Mellon JK, Griffiths TR, Gescher AJ. Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies. Eur J Cancer 2005;41:61-70. https://doi.org/10.1016/j.ejca.2004.09.028
  5. Mantovani G, Maccio A, Madeddu C, Mura L, Massa E, Gramignano G, et al. Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Cell Mol Med 2002;6:570-82. https://doi.org/10.1111/j.1582-4934.2002.tb00455.x
  6. Park S. The effects of high concentrations of vitamin C on cancer cells. Nutrients 2013;5:3496-505. https://doi.org/10.3390/nu5093496
  7. Chatterjee IB, Majumder AK, Nandi BK, Subramanian N. Synthesis and some major functions of vitamin C in animals. Ann N Y Acad Sci 1975;258:24-47. https://doi.org/10.1111/j.1749-6632.1975.tb29266.x
  8. Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in disease prevention and cure: an overview. Indian J Clin Biochem 2013;28:314-28. https://doi.org/10.1007/s12291-013-0375-3
  9. Mahdavi R, Faramarzi E, Seyedrezazadeh E, Mohammad-Zadeh M, Pourmoghaddam M. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res 2009;130:1-6. https://doi.org/10.1007/s12011-008-8309-2
  10. Harris HR, Orsini N, Wolk A. Vitamin C and survival among women with breast cancer: a meta-analysis. Eur J Cancer 2014; 50:1223-31. https://doi.org/10.1016/j.ejca.2014.02.013
  11. Lee KW, Lee HJ, Surh YJ, Lee CY. Vitamin C and cancer chemoprevention: reappraisal. Am J Clin Nutr 2003;78:1074-8. https://doi.org/10.1093/ajcn/78.6.1074
  12. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med 2014;6:222ra18. https://doi.org/10.1126/scitranslmed.3007154
  13. Carr AC, Vissers MC, Cook J. Relief from cancer chemotherapy side effects with pharmacologic vitamin C. N Z Med J 2014; 127:66-70.
  14. Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 2006;174:937-42. https://doi.org/10.1503/cmaj.050346
  15. Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat Med 2005;19:17-20. https://doi.org/10.1191/0269216305pm970oa
  16. Yeom CH, Choi YS, Ahn HY, Lee SH, Hwang IC. Oxidative stress level is not associated with survival in terminally ill cancer patients: a preliminary study. BMC Palliat Care 2014;13:14. https://doi.org/10.1186/1472-684X-13-14
  17. Yun YH, Heo DS, Heo BY, Yoo TW, Bae JM, Ahn SH. Development of terminal cancer prognostic score as an index in terminally ill cancer patients. Oncol Rep 2001;8:795-800.
  18. Manju V, Kalaivani Sailaja J, Nalini N. Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. Clin Biochem 2002;35:621-5. https://doi.org/10.1016/S0009-9120(02)00376-4
  19. Senthil K, Aranganathan S, Nalini N. Evidence of oxidative stress in the circulation of ovarian cancer patients. Clin Chim Acta 2004;339:27-32. https://doi.org/10.1016/j.cccn.2003.08.017
  20. Guo WD, Chow WH, Zheng W, Li JY, Blot WJ. Diet, serum markers and breast cancer mortality in China. Jpn J Cancer Res 1994;85:572-7. https://doi.org/10.1111/j.1349-7006.1994.tb02398.x
  21. Mayr VD, Dunser MW, Greil V, Jochberger S, Luckner G, Ulmer H, et al. Causes of death and determinants of outcome in critically ill patients. Crit Care 2006;10:R154. https://doi.org/10.1186/cc5086
  22. Hui D, dos Santos R, Chisholm G, Bansal S, Silva TB, Kilgore K, et al. Clinical signs of impending death in cancer patients. Oncologist 2014;19:681-7. https://doi.org/10.1634/theoncologist.2013-0457
  23. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010;49:1603-16. https://doi.org/10.1016/j.freeradbiomed.2010.09.006
  24. Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa MC, Ramirez-Tortosa CL, Granados-Principal S, Lorente JA, et al. Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates. Free Radic Res 2012;46:2-10. https://doi.org/10.3109/10715762.2011.635658
  25. Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa MC, Ramirez-Tortosa CL, Granados-Principal S, Fernandez-Navarro M, et al. Does chemotherapy-induced oxidative stress improve the survival rates of breast cancer patients? Antioxid Redox Signal 2011;15:903-9. https://doi.org/10.1089/ars.2011.3993
  26. Ozben T. Oxidative stress and apoptosis: impact on cancer therapy. J Pharm Sci 2007;96:2181-96. https://doi.org/10.1002/jps.20874
  27. Ratnam DV, Ankola DD, Bhardwaj V, Sahana DK, Kumar MN. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release 2006;113:189-207. https://doi.org/10.1016/j.jconrel.2006.04.015
  28. Suhail N, Bilal N, Khan HY, Hasan S, Sharma S, Khan F, et al. Effect of vitamins C and E on antioxidant status of breast-cancer patients undergoing chemotherapy. J Clin Pharm Ther 2012;37: 22-6. https://doi.org/10.1111/j.1365-2710.2010.01237.x
  29. Bhattacharyya J, Biswas S, Datta AG. Mode of action of endotoxin: role of free radicals and antioxidants. Curr Med Chem 2004;11:359-68. https://doi.org/10.2174/0929867043456098
  30. Hou CC, Lin H, Chang CP, Huang WT, Lin MT. Oxidative stress and pyrogenic fever pathogenesis. Eur J Pharmacol 2011; 667:6-12. https://doi.org/10.1016/j.ejphar.2011.05.075
  31. Lowe FJ, Luettich K, Gregg EO. Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective. Biomarkers 2013;18:183-95. https://doi.org/10.3109/1354750X.2013.777116
  32. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration. J Korean Med Sci 2007;22:7-11. https://doi.org/10.3346/jkms.2007.22.1.7