One-carbon metabolism biomarkers predict chemo-induced toxicities in CRC patients

Some biomarkers of one-carbon metabolism are associated with toxicities induced by chemotherapy in patients with stage II‒III colorectal cancer (CRC), suggests a study.

Chemotherapy-induced toxicities refer to toxicity-induced modifications of capecitabine treatment.

A total of 297 CRC patients receiving adjuvant capecitabine-based chemotherapy were included in the analysis. The authors determined the pretreatment plasma concentrations of the OCM biomarkers folate, vitamins B2, B6, B12, total homocysteine, methionine, serine, and glycine. They also examined whether associations varied as per methylenetetrahydrofolate reductase (MTHFR) C677T genotypes.

Hazard ratios (HRs) and 95 percent confidence intervals (CIs) were calculated using restricted cubic splines and Cox proportional hazards models, adjusted for age and sex.

Overall, 156 patients (53 percent) had toxicity-induced modifications of capecitabine treatment.

In the overall population, no association was observed between folate and toxicities. Higher folate concentrations even significantly correlated with a reduced risk of toxicities in patients with MTHFR C677T CT/TT genotype (HR, 0.75, 95 percent CI, 0.57‒0.98), but not in those with CC genotype (HR, 1.17, 95 percent CI, 0.84‒1.63).

Higher vitamin B2 concentrations were also associated with reduced toxicity risk (HR, 0.81, 95 percent CI, 0.67‒0.99), but higher glycine concentrations contributed to an increased risk of toxicities (HR, 1.87, 95 percent CI, 1.18‒2.94). The association between vitamins B6 and B12 and toxicities was nonlinear.

On the other hand, homocysteine, methionine, and serine did not correlate with toxicities.

“Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted,” the authors said.