TY - JOUR
T1 - Higher vitamin B6 status is associated with improved survival among patients with stage I–III colorectal cancer
AU - Holowatyj, Andreana N.
AU - Ose, Jennifer
AU - Gigic, Biljana
AU - Lin, Tengda
AU - Ulvik, Arve
AU - Geijsen, Anne J.M.R.
AU - Brezina, Stefanie
AU - Kiblawi, Rama
AU - van Roekel, Eline H.
AU - Baierl, Andreas
AU - Böhm, Jürgen
AU - Bours, Martijn J.L.
AU - Brenner, Hermann
AU - Breukink, Stéphanie O.
AU - Chang-Claude, Jenny
AU - de Wilt, Johannes H.W.
AU - Grady, William M.
AU - Grünberger, Thomas
AU - Gumpenberger, Tanja
AU - Herpel, Esther
AU - Hoffmeister, Michael
AU - Keulen, Eric T.P.
AU - Kok, Dieuwertje E.
AU - Koole, Janna L.
AU - Kosma, Katharina
AU - Kouwenhoven, Ewout A.
AU - Kvalheim, Gry
AU - Li, Christopher I.
AU - Schirmacher, Peter
AU - Schrotz-King, Petra
AU - Singer, Marie C.
AU - van Duijnhoven, Fränzel J.B.
AU - van Halteren, Henk K.
AU - Vickers, Kathy
AU - Vogelaar, Jeroen
AU - Warby, Christy A.
AU - Wesselink, Evertine
AU - Ueland, Per M.
AU - Ulrich, Alexis B.
AU - Schneider, Martin
AU - Habermann, Nina
AU - Kampman, Ellen
AU - Weijenberg, Matty P.
AU - Gsur, Andrea
AU - Ulrich, Cornelia M.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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. Am J Clin Nutr 2022;116:303–313.
AB - 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. Am J Clin Nutr 2022;116:303–313.
KW - colon cancer
KW - colorectal cancer
KW - HKr
KW - one-carbon metabolism
KW - PAR
KW - PLP
KW - rectal cancer
KW - recurrence
KW - survivorship
KW - vitamin B6
U2 - 10.1093/ajcn/nqac090
DO - 10.1093/ajcn/nqac090
M3 - Article
C2 - 35394006
AN - SCOPUS:85136306755
SN - 0002-9165
VL - 116
SP - 303
EP - 313
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 2
ER -
