The mechanism of elevated B12 in case of solid cancer is poorly understood5,6,20. Although our study cannot directly assess use of high Cbl levels as a nonspecific marker of cancer, our findings may be relevant to the clinical interpretation of such high levels. Patients were excluded if they had a cancer diagnosis before the date of the plasma Cbl measurement. The overall cancer risk increased with higher Cbl levels and with a peak during the first year of follow-up (Cbl 601–800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76, P < 0.001; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88, P < 0.001). Follow-up was limited at 60 months. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. The DCR was used to identify subsequent diagnoses of cancer from 1998 to 2010 among patients with a Cbl test result in the LABKA database. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Clin. Careers, Unable to load your collection due to an error. Screen. Serefhanoglu S, Aydogdu I, Kekilli E, Ilhan A, Kuku I. Ann Hematol. Disclaimer. Clin. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use. The categorical data were presented as absolute values and as percentages and were compared using Chi-squared test. Simonsen, K. et al. Because high plasma Cbl levels also have been associated with other conditions (19), we assessed cancer risk in relation to selected morbidities, categorized according to ICD-10 codes (see Supplementary Table 1, available online). Med. 2). & Nexo, E. Unexpected high plasma cobalamin/Proposal for a diagnostic strategy. Arendt, J. F. B. While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. J. Haematol. Careers. Patients in whom active screening should be discussed need to be better targeted to allow early diagnosis and limit unnecessary investigations. F.C. No consensus exists concerning a diagnostic strategy in case of incidental finding of elevated B125,18,19. Association study between genome-wide significant variants of vitamin B12 metabolism and gastric cancer in a han Chinese population: Unexpected Role of Vitamin B12 Metabolism Genes. Patients were classified as inpatients or outpatients if they were admitted and/or had a hospital outpatient clinic visit up to 30 days before or 7 days after Cbl measurement. When we examined the association between high Cbl levels and specific cancer types within the first year of follow-up (Figure 2) (SIRs and 95% CIs for Cbl levels >800 pmol/L), we found associations with gastric (SIR = 13.24; 95% CI = 7.23 to 22.21; P < .001), colorectal (SIR = 5.48; 95% CI = 4.01 to 7.31; P < .001), liver (SIR = 40.70; 95% CI = 25.50 to 61.62; P < .001), pancreatic (SIR = 15.57; 95% CI = 10.34 to 22.50; P < .001), lung (SIR = 9.27; 95% CI = 7.24 to 11.69; P < .001), renal (SIR = 9.56; 95% CI = 4.58 to 17.58; P < .001), urinary bladder (SIR = 5.34; 95% CI = 3.11 to 8.55; P < .001), lymphatic leukemia (SIR = 8.88; 95% CI = 3.56 to 18.29; P < .001), myeloid malignancies (SIR = 105.73; 95% CI = 81.24 to 135.28; P < .001), non-Hodgkin lymphoma (SIR = 6.64; 95% CI = 3.31 to 11.89; P < .001), and multiple myeloma (SIR = 16.08; 95% CI = 7.70 to 29.58; P < .001). Als hoch gelten Blutwerte oberhalb von 900 pg/ml, in einigen Fällen werden jedoch Werte weit im vier- oder sogar fünfstelligen Bereich gemessen. COBALAMIN (VITAMIN B12) AS A TUMOR MARKER FOR… 1741 RESULTS The ages of patients included in group I ranged between 39 to 71years with a Mean ± SD of (56.88 ± 7.67) years, of sharing sensitive information, make sure you’re on a federal Elevated vitamin B12 (also known as hypervitaminosis B12 or hypercobalaminemia) is most important as a diagnostic and prognostic marker for malignant disease 1,3. For hematological cancers and smoking- and alcohol-related cancers, the standardized incidence ratios remained elevated for more than 5 years of follow-up, although for hematological cancers, this was the case only for patients with Cbl levels greater than 800 pmol/L (Supplementary Table 2, available online). In the absence of B12 ≥ 1000 ng/L, T1 was randomly selected between the first and the penultimate B12 measurement. Some causes can be explored with simple investigations (blood count, renal function evaluation, liver cytolysis and cholestasis parameters, and liver echography) but solid cancer exploration often requires imaging or endoscopic examinations. Epub 2014 Apr 10. Accessibility 17, 1 (2017). CAS  Minimally Invasive Surg. The DNRP includes the patient’s civil registration number, hospital admission and discharge date, date of hospital outpatient visit, and up to 20 diagnoses coded by physicians, including a primary diagnosis representing the main reason for the inpatient or outpatient hospital contact. In clinical practice, measurement of total plasma Cbl is requested widely for the biochemical assessment of Cbl deficiency (2). Long- and short-term effects of tobacco smoking on circulating concentrations of B vitamins. In the analyses, we first excluded patients receiving Cbl therapy. The incidence of elevated-B12-related causes could be underestimated due to the retrospective and non-interventional nature of the study. Because we specifically focused on high Cbl levels, we were able to demonstrate associations with cancer, including types not previously associated with high Cbl levels, such as cancers of the pancreas and urinary bladder and multiple myeloma. We identified all patients in the LABKA database with a plasma Cbl measurement of greater than 200 pmol/L [lower reference limit in Northern Denmark = 271 pg/mL (27)] recorded from 1998 through 2009. Compared with the reference NN group, the EE group was associated with the occurrence of solid cancers with or without metastases (p < 0.001 and p < 0.001, respectively), contrary to the EN group (p = 0.56 and p = 0.38, respectively). Patients with cancer have been reported to show elevated plasma concentrations of vitamin B12, thus causing uncertainties regarding safety of vitamin B12. This protein originates from a variety of tissues, but its physiological function remains unknown (32). The site of primary cancer (according to the International Classification of Diseases for Oncology classification), presence of metastasis and site of metastasis were collected. J. Inborn Errors Metab. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Lab. To avoid this, we included the sex of patients as a variable of adjustment in the survival model and, finally, sex did not significantly influence the occurrence of cancer at 60 months. Solid cancers and metastases sites are presented in Table S1, supplemental material. It is elevated in patients with some cancer types (6,10,11) and has been suggested as a marker for disease progression (6,10). Vlasveld, L. T., Bos, G. M. J., Ermens, A. To assess possible confounding from underlying diseases, we obtained data on all diagnoses before Cbl measurement from the DNRP and grouped them according to ICD-10 codes. This will help them manage your care and keep you safe. The B12 measurements were centralized in the biochemistry laboratory of Angers University Hospital. However, the latter studies are limited by their cross-sectional design, and only one study included a comparison group of patients with normal and low plasma Cbl levels (3). Bull. Vitamin B12 is required for the . Laboratory reference intervals for Northern Denmark (updated 24th of January 2011). The cohort study included 90 HCC patients who were consecutively admitted to the Chi-Mei Hospital, Taiwan, from April 2005 to December 2006. The prevalence ranges from 1.2% to 18%, depending on study population and cutoff values for defining high B12 levels ().These persons have gained attention in recent years, because an association between elevated B12 levels and cancer has been reported in several studies. Cobalamin (Vitamin B12) Bei Vitamin B12 (Synonyme: Cobalamin, Extrinsic-Factor) handelt es sich um einen lebenswichtigen Nahrungsbestandteil aus dem Vitamin B-Komplex. Feline hyperammonemia associated with functional cobalamin deficiency: A case report. 16, 235 (2015). Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study. Arshad, M. et al. The second hypothesis is that of the release of haptocorrins by the granulocytic cells involved in the anti-tumor response. We also obtained results for specific cancers. Cancer risk diagnosed after a plasma cobalamin (Cbl) measurement according to sex, follow-up interval, age, cancer group, and plasma Cbl levels*. Accessibility C.L., A.G., O.C., A.P. The prognostic nature of elevated B12 in solid cancers suggested the question of a possible link with the tumor mass or the capacity for proliferation20. However, to our knowledge, no study has evaluated this association according to the persistence of this B12 elevation. All statistical tests were two-sided. Rev. Sviri, S. et al. 2023 May;46(5):1276-1286. doi: 10.1038/s41440-023-01218-w. Epub 2023 Feb 20. Patients with B12 ≥ 1000 ng/L at T1 were selected and matched with a control group. Für Säuglinge und Kleinkinder sind Vitamin B12-Tropfen oder -Sprays natürlich besser geeignet als Tabletten, während z. We set the period of at least 1 month between the 2 measurements to allow normalization of B12 in case of acute transient elevation. Zittoun J, Zittoun R, Marquet J, Sultan C. The three transcobalamins in myeloproliferative disorders and acute leukaemia. It can also be made in a lab and is often taken with other B vitamins. Elevated VitB(12) levels in concurrence with AFP levels serve as the prognostic factors predictive for poor survival of HCC patients. Finally, we did not include concurrent blood test results on other biochemical parameters. Most studies on normal or low Cbl levels in relation to cancer have been negative (12–16), except for some studies showing associations between increasing Cbl levels and lung and prostate cancer (17,18). FOIA The age of the patients was similar in the 3 groups (Table 1). Would you like email updates of new search results? Karin Amrein, Mario Scherkl, … Oliver Malle, Arash Shirvani, Tyler Arek Kalajian, … Michael F. Holick, Armin Zittermann, Heiner K. Berthold & Stefan Pilz, Astrid Lipplaa, Ricardo Fernandes, … Pippa G. Corrie, Deirdre K. Tobias, Aditi Hazra, … Samia Mora, Visalini Nair-Shalliker, Albert Bang, … David P. Smith, M. Rebecca Heiner-Fokkema, Ineke J. Riphagen, … Wilhelmina H. A. de Jong, Agustina A. M. B. Hastuti, Marta Costas-Rodríguez, … Frank Vanhaecke, Scientific Reports official website and that any information you provide is encrypted The https:// ensures that you are connecting to the Elevated serum VitB(12) levels of HCC patients were associated with reduced levels of albumin, hemoglobin, red blood cells count, and glutamate-pyruvate transaminase (GPT) (P < 0.05). Control patients were randomly selected among those with B12 < 1000 ng/L at T1 and T2, with a ratio 1:1, matching for sex, age and the number of B12 measurements (2, 3, ≥ 4) during the study period. As a library, NLM provides access to scientific literature. Wang, Z. et al. Dis. The proportional hazard assumption was checked with 2 different methods: graphically by plotting the log(minuslog) curves and by studying the interaction with time. contributed to analysis and interpretation of data and critically revised the manuscript for important intellectual content. Podzolkov VI, Dragomiretskaya NA, Dambaeva OT, Auvinen ST, Medvedev ID. Frenkel, E. P., White, J. D., Reisch, J. S. & Sheehan, R. G. Comparison of two methods for radioassay of vitamin B12 in serum. However, we find it unlikely that the finding of elevated Cbl levels in itself led to increased surveillance for cancer, although this statement cannot be further assessed. An elevated B12 is generally defined as a level higher than the upper limit of the normal range, around 1000 ± 100 ng/L (738 ± 73.8 pmol/L)2,3,4. 2017 Mar 9;60(1):31-39. eCollection 2017 Mar. An official website of the United States government. We conducted this cohort study using population-based Danish medical registries. 89, 812–819 (2008). Ein zu hoher Homocysteinspiegel im Blut kann Schädigungen der Blutgefäße nach sich ziehen [3]. A number of different diseases have been suggested as causing high Cbl levels (19), but common to most of them is that the pathogenesis involving elevated Cbl levels is not fully understood. 40: 158-65. 5, 2 (2016). Nutrition and clinical pathological data were collected. Indeed, the frequency of incident diagnoses of chronic liver diseases (32/144, 22.2%) and myeloid blood malignancies (25/144, 17.4%) in the EE group also confirmed the interest in screening these pathologies in case of persistent elevated B125,18,19. These results could help to select patients in whom the screening for solid cancers would be of interest. Hypercobalaminemia (high serum vitamin B12 levels) is a frequent and underestimated anomaly. Incident solid cancer was diagnosed in 30/144 (20.8%) patients in the EE group, 12/200 (6.0%) in the EN group and 13/344 (3.8%) in the NN group (p < 0.001).

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