Higher vitamin B6 status is associated with improved survival among patients with stage I-III colorectal cancer

Abstract

Background: Folate-mediated 1-carbon metabolism requires several nutrients, including vitamin B6. Circulating biomarker concentrations 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 6 prospective patient cohorts in the international FOCUS (folate-dependent 1-carbon metabolism in colorectal cancer recurrence and survival) Consortium. Preoperative blood samples were used to measure vitamin B6 status by the direct marker pyridoxal 5'-phosphate (PLP), as well as the functional marker HK-ratio (HKr)[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 concentrations, tumor site, stage, and cohort.

Results: After a median follow-up of 3.2 y 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: 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.

Keywords: HKr; PAR; PLP; colon cancer; colorectal cancer; one-carbon metabolism; rectal cancer; recurrence; survivorship; vitamin B6.

FIGURE 1

Study enrollment flow chart for the FOCUS consortium.

FIGURE 2

Unadjusted associations between PLP concentrations and HKr with overall survival (A), disease-free survival (B), and risk of recurrence (C) by tertiles among stage I–III colorectal cancer patients from the FOCUS Consortium. PLP, T1: 5.52–31.1 nmol/l; T2: 31.2–52.1 nmol/l; T3: >52.1 nmol/l. HKr, T1: −7.138 to −1.636; T2: −1.635 to −1.222; T3: >−1.222. FOCUS, folate-dependent 1-carbon metabolism in colorectal cancer recurrence and survival; PLP, pyridoxal 5′-phosphate; HAA, 3′-hydroxyantranilic acid; HKr, 3′-hydroxykynurenine: [hynurenic acid + xanturenic acid + 3′ anthranilic acid + anthranilic acid.