BACKGROUND
Folate-mediated one-carbon metabolism requires several nutrients, including vitamin B6. Circulating levels of biomarkers indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients.
OBJECTIVES
We investigated survival outcomes in relation to vitamin B6 status in prospectively followed CRC patients.
METHODS
A total of 2031 patients with stage I-III CRC participated in six prospective patient cohorts in the international FOCUS Consortium. Preoperative blood samples were used to measure vitamin B6 status by the direct marker pyridoxal 5'-phosphate, PLP, as well as functional marker the HK-ratio (3'-hydroxykynurenine: [kynurenic acid + xanthurenic acid + 3'-hydroxy anthranilic acid + anthranilic acid]). Using Cox proportional hazards regression, we examined associations of vitamin B6 status with overall survival (OS), disease-free survival (DFS), and risk of recurrence, adjusted for patient age, sex, circulating creatinine levels, tumor site, stage, and cohort.
RESULTS
After a median follow-up of 3.2 years for OS, higher preoperative vitamin B6 status as assessed by PLP and the functional marker HKr was associated with 16-32% higher all-cause and disease-free survival, although there was no significant association with disease recurrence (doubling in PLP concentration: hazard ratio, HROS, 0.68; 95% CI, 0.59,0.79; HRDFS, 0.84; 95% CI, 0.75,0.94; HRRecurrence, 0.96; 95% CI, 0.84,1.09; HKr: HROS, 2.04; 95% CI, 1.67,2.49; HRDFS, 1.56; 95% CI, 1.31,1.85; HRRecurrence, 1.21; 95% CI, 0.96,1.52). The association of PLP with improved OS was consistent across colorectal tumor site (right-sided colon: HROS, 0.75; 95% CI, 0.59,0.96; left-sided colon: HROS, 0.71; 95% CI, 0.55,0.92; rectosigmoid junction and rectum: HROS, 0.61; 95% CI, 0.47,0.78).
CONCLUSION
Higher preoperative vitamin B6 status is associated with improved OS among stage I-III CRC patients.