Establishing a Method for Measuring Serum Methylmalonic Acid and Application to Women with a History of Breast Cancer

摘要

Serum concentrations of methylmalonic acid (MMA), a dicarboxylic acid and intermediate in the conversion of propionic acid to succinic acid, are elevated if there is deficiency of cobalamin (vitamin B12) at the tissue level. Measurement of serum MMA may be the best way to assess vitamin B12 status. Early diagnosis of vitamin B12 deficiency may improve patient treatment and prevent later sequelae. A method of measuring serum MMA using gas chromatography/mass spectroscopy was developed in the laboratory. The new test method correlated well with values obtained in a reference laboratory assay. The method was used to determine the reference range in a normal female population. Frozen sera specimens from female patients with breast cancer were assayed for MMA, and compared with the normal population using the t-test statistic. A statistically significant (p<0.05) difference was found between the normal and breast cancer group 2 (loca/recurrent cancer) population, with increased levels of serum MMA in the breast cancer population. The breast cancer population was also stratified by the extent of cancer. No statistically significant differences were detected between the breast cancer subgroups, but the differences between the normal population and the breast cancer subgroups were most significant for the patients with recurrent disease. The correlation between levels of the breast cancer tumor marker CA27.29 and serum MMA was highly significant. Results of methylmalonic acid serum analysis suggests that vitamin B12 deficiency at the tissue level is common among patients with recurrent or local breast cancer.