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Int. J. Mol. Sci. 2016, 17(7), 1032;

Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma

Department of Public Health, Qingdao University Medical College, No. 38 Dengzhou Road, Qingdao 266021, China
Department of Public Health, Yanbian University Medical College, No. 977 Gongyuan Road, Yanji 133002, China
Department of Oncology, Shengli Oil-Field Central Hospital, No. 31 Jinan Road, Dongying 257000, China
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju 501-746, Korea
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: William Chi-shing Cho
Received: 30 April 2016 / Revised: 16 June 2016 / Accepted: 23 June 2016 / Published: 30 June 2016
(This article belongs to the Special Issue Liquid Biopsy for Clinical Application)
Full-Text   |   PDF [226 KB, uploaded 30 June 2016]


Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients’ clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15–0.60), 0.33 (0.17–0.65), and 0.19 (0.09–0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02–3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results. View Full-Text
Keywords: folate; vitamin B12; hepatocellular carcinoma; susceptibility; tumor progression folate; vitamin B12; hepatocellular carcinoma; susceptibility; tumor progression
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Cui, L.-H.; Quan, Z.-Y.; Piao, J.-M.; Zhang, T.-T.; Jiang, M.-H.; Shin, M.-H.; Choi, J.-S. Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma. Int. J. Mol. Sci. 2016, 17, 1032.

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