Journal List > Korean J Health Promot > v.17(4) > 1089928

Korean J Health Promot. 2017 Dec;17(4):282-288. Korean.
Published online December 28, 2017.  https://doi.org/10.15384/kjhp.2017.17.4.282
Copyright © 2017 Korean Society for Health Promotion and Disease Prevention
Prognostic Role of Serum Vitamin B12 in Solid Tumor Patients
Hye Kyung Oh,1 Jee Young Lee,2 Seong Woo Yoon,2 Wan Kyu Eo,3 and Sung Nim Han1,4
1Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.
2Department of Internal Korean Medicine, Korean Medicine Cancer Center, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
3Department of Hematology/Medical Oncology, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
4Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Korea.

Corresponding author: Sung Nim Han, PhD. Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. Tel: +82-2-880-6836, Fax: +82-2-884-0305, Email: snhan@snu.ac.kr
Received August 30, 2017; Accepted October 13, 2017.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Background

Serum vitamin B12 has been suggested as one of the cancer diagnostic markers and predictors for survival in cancer patients. In this study, we investigated the relationship between vitamin B12 and tumor progression.

Methods

Solid tumor patients who had serum vitamin B12 levels and radiologic test follow-up were included in the study. A total of 55 patients were included. Receiver operating characteristic analysis was performed to determine the cut-off value of vitamin B12 for tumor progression. Kaplan-Meier method and Cox proportional hazard model for time to progression (TTP) were performed. Subgroup analysis was performed on patients with or without liver lesion (hepatocellular carcinoma and liver metastasis).

Results

The cut-off value of vitamin B12 for tumor progression prediction was 691.4 pg/mL, the sensitivity was 57.1% and the specificity was 59.3%. Patients with vitamin B12≥691.4 pg/mL had shorter median TTP (2.1 months vs. 3.4 months, P=0.011). In subgroup analysis of patients without liver lesion, median TTP was significantly shorter in patients with vitamin B12≥691.4 pg/mL (1.6 months vs. 6.3 months, P=0.021), while there was no significant difference in TTP among the patients with liver lesion. Higher vitamin B12 level (≥691.4 pg/mL) was an independent prognostic factor for tumor progression (adjusted hazard ratio 2.4, 95% confidence interval 1.2–4.8, P=0.019).

Conclusions

Serum vitamin B12 level can be used as a predictor of tumor progression in patients with solid tumors especially in patients without liver lesion. Additional large scale prospective studies are required to confirm this.

Keywords: Vitamin B12; Biomarkers; Neoplasms; Disease progression

Figures


Figure 1
Progression receiver operating characteristic curve for vitamin B12. 691.4 pg/mL was the cut-off value for serum vitamin B12 level related with tumor progression.
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Figure 2
Kaplan-Meier curve for time to progression (TTP). (A) All patients. Median TTP in patients with vitamin B12<691.4 pg/mL and in patients with vitamin B12≥691.4 pg/mL was 3.4 months (95% confidence interval [CI] 1.8–5.0) and 2.1 months (1.9–2.3), respectively (P=0.011). (B) Non-liver lesiona group. Median TTP in patients with vitamin B12<691.4 pg/mL and in patients with vitamin B12≥691.4 pg/mL was 6.3 months (2.9–9.7) and 1.6 months (0.0–3.5), respectively (P=0.021). (C) Liver lesion group. Median TTP in patients with vitamin B12<691.4 pg/mL and in patients with vitamin B12≥691.4 pg/mL was 1.8 months (1.0–2.6) and 2.1 months (2.0–2.3), respectively (P=0.816). P values by log-rank test.
aLiver lesion included hepatocellular carcinoma and liver metastasis.
Click for larger image

Tables


Table 1
Characteristics of patients
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Table 2
Changes in serum vitamin B12 levels according to tumor response
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Table 3
Risk for TTP according to vitamin B12 level
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References
1. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician 2003;67(5):979–986.
2. Lechner K, Födinger M, Grisold W, Püspök A, Sillaber C. Vitamin B12 deficiency. New data on an old them. Wien Klin Wochenschr 2005;117(17):579–591.
3. Arendt JF, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS One 2012;7(9):e45979
4. Arendt JF, Nexo E. Unexpected high plasma cobalamin: proposal for a diagnostic strategy. Clin Chem Lab Med 2013;51(3):489–496.
5. Arendt JF, Pedersen L, Nexo E, Sørensen HT. Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study. J Natl Cancer Inst 2013;105(23):1799–1805.
6. Arendt JF, Farkas DK, Pedersen L, Nexo E, Sørensen HT. Elevated plasma vitamin B12 levels and cancer prognosis: a population-based cohort study. Cancer Epidemiology 2016;40:158–165.
7. Lin CY, Kuo CS, Lu CL, Wu MY, Huang RF. Elevated serum vitamin B(12) levels in association with tumor markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma. Nutr Cancer 2010;62(2):190–197.
8. Kelly L, White S, Stone PC. The B12/CRP index as a simple prognostic indicator in patients with advanced cancer: a confirmatory study. Ann Oncol 2007;18(8):1395–1399.
9. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–247.
10. Tavares F. Is the B12/CRP index more accurate than you at predicting life expectancy in advanced cancer patients? J Pain Symptom Manage 2010;40(1):e12–e13.
11. Ryg J, Nybo M, Hallas J. Cancer incidence in persons with elevated cobalamin levels. Eur J Clin Invest 2013;43(6):557–561.
12. Schwettmann L, Berbu S. Reference interval and status for serum folate and serum vitamin B12 in a Norwegian population. Clin Lab 2015;61(8):1095–1100.
13. Bor MV, Lydeking-Olsen E, Møller J, Nexø E. A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am J Clin Nutr 2006;83(1):52–58.
14. Salles N, Herrmann F, Sakbani K, Rapin CH, Sieber C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr Soc 2005;53(5):917–918.
15. Duffy MJ. Tumor markers in clinical practice: a review focusing on common solid cancers. Med Princ Pract 2013;22(1):4–11.
16. Wu AH, Sell S. Markers for hepatocellular carcinoma. Immunol Ser 1990;53:403–422.
17. Zhang K, Song P, Gao J, Li G, Zhao X, Zhang S. Perspectives on a combined test of multi serum biomarkers in China: towards screening for and diagnosing hepatocellular carcinoma at an earlier stage. Drug Discov Ther 2014;8(3):102–109.
18. Daniele B, Bencivenga A, Megna AS, Tinessa V. Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 2004;127 5 suppl 1:S108–S112.
19. Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 2006;101(3):524–532.
20. Yu J, Zhang S, Zhao B. Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer. Mol Clin Oncol 2016;4(3):441–449.
21. Du R, Cheng D, Lin L, Sun J, Peng K, Xu Y, et al. Association between serum CA 19-9 and metabolic syndrome: a cross-sectional study. J Diabetes 2017;9(11):1040–1047.
22. Virgilio E, Proietti A, D'Urso R, Cardelli P, Giarnieri E, Montagnini M, et al. Measuring intragastric tumor markers in gastric cancer patients: a systematic literature review on significance and reliability. Anticancer Res 2017;37(6):2817–2821.
23. Solomon LR. Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev 2007;21(3):113–130.
24. Collin SM, Metcalfe C, Refsum H, Lewis SJ, Zuccolo L, Smith GD, et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2010;19(6):1632–1642.
25. Lildballe DL, Nguyen KQ, Poulsen SS, Nielsen HO, Nexo E. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma. Eur J Surg Oncol 2011;37(1):72–79.
26. Sysel AM, Valli VE, Nagle RB, Bauer JA. Immunohistochemical quantification of the vitamin B12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts. Anticancer Res 2013;33(10):4203–4212.
27. Donkena KV, Yuan H, Young CY. Vitamin Bs, one carbon metabolism and prostate cancer. Mini Rev Med Chem 2010;10(14):1385–1392.
28. Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem 2003;36(8):585–590.
29. Fenech MF, Dreosti IE, Rinaldi JR. Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis 1997;18(7):1329–1336.
30. Kapiszewska M, Kalemba M, Wojciech, U, Milewicz T. Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study. J Nutr Biochem 2005;16(8):467–478.