Holotranscobalamin Deficiency and Hyperhomocysteinemia Are Common in Newly Diagnosed Cancer Patients.
Authors: Nguyen Hanh T.H. , Shah Vinay M. , Ramos Mercedita , Tisman Glenn 
Published: October 2019

Abstract
We measured serum folic acid, total serum vitamin B12, B12 complexed to transcobalamin as holotranscobalamin (HTCII), total homocysteine (tHcy), serum creatinine and estimated creatinine clearance (eCrCl) in 37 cancer patients presenting with newly diagnosed solid tumors. Serum HTCII was measured by the glass adsorption technique developed in this laboratory (Vu, T et al. Am J. Hem 42: 202–211 1993). Pearson’s r values were calculated for tHcy as a function of serum folate, total B12, HTCII, or eCrCl. R values reflect the degree of linear relationship between two variables. We found that 15 of 37 (40.5%) newly diagnosed and untreated cancer patients had serum homocysteine levels above 12 μM/L. The mean tHCY = 11.43 μM/L, median = 10.7 μM/L, range = 2.5 to 22.4 μM/L. One of the 36 (2.8%) patients for whom folate data was available had folate deficiency (folate = 4.2 ng/mL; pancreatic cancer). Mean folate = 19.35 ng/mL, median = 20.0 ng/mL, range = 4.2–40.2 ng/mL. Serum folate was only weakly inversely related to tHcy (r = −0.29551). Serum eCrCl was strongly inversely related to tHcy (r = −0.57927, p < 0.0002). Twenty-seven of 37 patients (73%) had a low creatinine clearance (<74 ml/min). The mean eCrCl = 63.3 mL/min, median = 62 mL/min, range = 24–131 ml/min. Serum HTCII and total B12 levels were moderately inversely related to tHcy (r = −0.3718 for HTCII, r = −0.33085 for total B12). Fourteen of 28 (50.0%) cancer patients had cobalamin insufficiency as their HTCII (the metabolically active form of B12) was measured at levels of <70 pg/mL. Only 1 of 37 patients (2.7%) in a group that included the HTCII deficient patients was deficient in total B12 at the <200 pg/ml level. Seven of 37 (18.9%) patients in this group were deficient in total B12 at the <300 pg/mL level. Four of the 14 HTCII deficient patients (28.6%) were diagnosed as B12 deficient at the <300 pg/mL level, while no patients were B12 deficient at the <200 pg/ml level. The routine measurement of total B12 levels (deficiency <300 pg/mL) identified less than one third of patients with HTCII deficiency. HTCII deficiency is frequent and not measurable by total B12, the most widely used test. Total homocysteine is frequently elevated in cancer patients and may cause thrombophilia and osteoporosis. Total homocysteine in cancer patients is more a function of renal failure (as indicated by low eCrCl) than of folate or B12 deficiency. It appears that serum folate deficiency in the new millenium (post January 1998 when the FDA required all enriched grain products to contain 140 mcg of folic acid per 100 grams) is uncommon even in cancer patients with their increased demand for folate. The effects of vitamin B12 supplements on chemotherapy toxicity and treatment outcome for newly diagnosed cancer patients about to undergo therapy should be studied. B12 prophylaxis for cancer prevention warrants study as well since breast cancer incidence may be 2.5–4 fold higher for B12 deficient patients (Wu, K. et al. Cancer Epidemiol. 1999. 8:209–17). Supported in part by a grant from ThinkTwice Technologies. This work is dedicated to the memory of Dr. Victor Herbert whose teachings continue to inspire our research efforts.