Serum MMA levels predict long-term mortality in cancer survivors

Serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, appears to contribute to long-term mortality in adult cancer survivors, particularly in those with higher levels of serum cobalamin, suggests a study.

Data from 1988 cancer survivors aged ≥20 years were analysed. The authors assessed patients from the National Health and Nutrition Examination Survey and followed them until 31 December 2019. They estimated hazard ratios (HRs) and 95 percent confidence intervals (CIs) for mortality risk assessment using weighted Cox proportional hazard regression.

Finally, the authors performed genomic analysis to identify MMA metabolism-related genes associated with early death in a 33-cancer-type cohort from The Cancer Genome Atlas.

A total of 1,988 participants were included, of whom 872 died over a 10-year follow-up. Survivors with increased levels of serum MMA showed a significantly higher mortality risk in the long term (tertile 3 vs tertile 1: adjusted HR, 1.37, 95 percent CI, 1.11‒1.70; p_trend<0.001).

Serum, dietary, and supplement of cobalamin had no significant associations with cancer survivor mortality (p_trend>0.143 for each). However, MMA-related death was significant among those without deficiency.

When cobalamin and MMA categories were combined, participants with MMA >250 nmol/L and cobalamin >295.1 pmol/L had significantly higher risk of all-cause mortality (adjusted HR, 2.06, 95 percent CI, 1.60‒2.65) than those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L.

In addition, reduced transcriptional levels of MMA metabolism-related genes, which suggest a lower mitochondrial MMA metabolism capability, correlated with a poor prognosis in some cancer types.

“These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency,” the authors said.