Why the study?
One-carbon metabolism is targeted by capecitabine, but its biomarker concentrations had not been evaluated in relation to capecitabine-induced toxicities in stage II-III colorectal cancer.
Are pretreatment one-carbon metabolism biomarker concentrations associated with capecitabine-induced toxicities in patients with stage II-III colorectal cancer?
Are pretreatment one-carbon metabolism biomarker concentrations associated with capecitabine-induced toxicities in patients with stage II-III colorectal cancer?
Pretreatment levels of vitamin B2 and glycine, as well as folate in specific MTHFR genotypes, are associated with the risk of capecitabine-induced toxicities in colorectal cancer patients.
Introduction One-carbon metabolism (OCM) is a target of the chemotherapeutic agent capecitabine. We investigated OCM biomarker concentrations in relation to capecitabine-induced toxicities in patients with stage II-III colorectal cancer (CRC). Method Within a prospective cohort, 297 patients receiving adjuvant capecitabine-based chemotherapy were included. Pretreatment plasma concentrations of the OCM biomarkers folate, vitamin B2, vitamin B6, vitamin B12, total homocysteine, methionine, serine, and glycine were determined. We also investigated whether associations differed according to MTHFR C677T genotypes. Chemotherapy-induced toxicities were defined as toxicity-induced modifications of capecitabine treatment. To allow for inspection of shapes of the associations, restricted cubic splines (RCS) and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age and sex. Results In total, 156 (53%) patients experienced toxicity-induced modifications of capecitabine treatment. Folate was not associated with toxicities in the overall population. Higher folate concentrations were associated with a lower risk of toxicities in patients with MTHFR C677T CT/TT genotype (HR perdoubling 0.75, 95%CI 0.57-0.98) but not in patients with CC genotype (HR perdoubling 1.17, 95%CI 0.84-1.63). Higher concentrations of vitamin B2 were associated with a lower risk of toxicities (HR perdoubling 0.81 95%CI 0.67-0.99), whereas higher glycine concentrations were associated with a higher risk of toxicities (HR perdoubling 1.87, 95%CI 1.18-2.94). The association between vitamin B6 and vitamin B12 and toxicities appeared nonlinear. Homocysteine, methionine, and serine were not associated with toxicities. Conclusions Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted.
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Zwart et al. (2026) studied this question.
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