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Hyperhomocysteinemia in Cancer Patients with Thrombosis is Not Associated With Methylene Tetrahydrofolate Reductase Gene Mutations and Can Be Down Regulated by Low Molecular Weight Heparin Treatment
Author(s) -
Hoppensteadt Debra,
Neville B,
Cunanan J,
Iqbal O,
Demir M,
Fareed J,
Deitcher S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a650
Subject(s) - methylenetetrahydrofolate reductase , hyperhomocysteinemia , heparin , medicine , thrombosis , low molecular weight heparin , cancer , homocysteine , methylene blue , gene , cancer research , chemistry , biochemistry , allele , photocatalysis , catalysis
Methylene tetrahydrofolate reductase (MTHFR) gene mutations, nutritional factors, and anticancer drugs are primarily responsible for the observed hyper‐homocysteinemia in cancer patients. In three groups of 210 patients who were diagnosed with cancer and thrombosis and in a group of medical patients (cancer free) with thrombosis enrolled in a treatment study with low molecular weight heparin (LMWH), (Reviparin, n=90), blood levels of homocysteine were measured using an ELISA method (Diazyme Laboratories, San Diego, CA). Molecular methods utilizing PCR were used to measure MTHFR (677 and 1298) variants. On a cumulative basis the cancer patients with thrombosis exhibited a relatively higher level of homocysteine (12.8±4.9; range 2.2–39.4 uM/L) in comparison to normal (n=140, 4.8±3.9; range 2.8=6.9 uM/L) and medical patients with thrombosis (5.3±3.1; range 2.1–9.8 uM/L). Of the 210 cancer patients profiled for the molecular analysis 42/210 (20%) were positive for the 677 variant and 24/210 (11%) were positive for the 1298 variant. One group of cancer patients (n=72) was treated with a LMWH for 4–6 weeks. Blood samples from these patients showed a down‐regulation of homocysteine levels (4.8±2.5 uM/L). These results suggest that cancer patients with thrombosis exhibited a relatively higher level of circulating homocysteine levels which are unrelated to a molecular defect in MTHFR.