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

HKr PAR PLP colon cancer colorectal cancer one-carbon metabolism rectal cancer recurrence survivorship vitamin B6

Journal

The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027

Informations de publication

Date de publication:
04 08 2022
Historique:
received: 27 09 2021
accepted: 04 04 2022
pubmed: 9 4 2022
medline: 6 8 2022
entrez: 8 4 2022
Statut: ppublish

Résumé

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. We investigated survival outcomes in relation to vitamin B6 status in prospectively followed CRC patients. 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. 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). Higher preoperative vitamin B6 status is associated with improved OS among stage I-III CRC patients.

Sections du résumé

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.

Identifiants

pubmed: 35394006
pii: S0002-9165(22)00037-5
doi: 10.1093/ajcn/nqac090
pmc: PMC9348990
doi:

Substances chimiques

Biomarkers 0
Pyridoxal Phosphate 5V5IOJ8338
Carbon 7440-44-0
Vitamin B 6 8059-24-3
Folic Acid 935E97BOY8

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

303-313

Subventions

Organisme : NHGRI NIH HHS
ID : T32 HG008962
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA189184
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA206110
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207371
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD043483
Pays : United States

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

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Auteurs

Andreana N Holowatyj (AN)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Jennifer Ose (J)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

Biljana Gigic (B)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany.

Tengda Lin (T)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

Arve Ulvik (A)

BEVITAL, Bergen, Norway.

Anne J M R Geijsen (AJMR)

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Stefanie Brezina (S)

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria.

Rama Kiblawi (R)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.
Medical Faculty, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.

Eline H van Roekel (EH)

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, The Netherlands.

Andreas Baierl (A)

Department of Statistics and Operations Research, University of Vienna, Austria.

Jürgen Böhm (J)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

Martijn J L Bours (MJL)

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, The Netherlands.

Hermann Brenner (H)

Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Stéphanie O Breukink (SO)

Department of Surgery, GROW School for Oncology and Development Biology, Maastricht University, The Netherlands.

Jenny Chang-Claude (J)

Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg Germany.

Johannes H W de Wilt (JHW)

Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Radboud University Medical Center, The Netherlands.

William M Grady (WM)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Thomas Grünberger (T)

Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria.

Tanja Gumpenberger (T)

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria.

Esther Herpel (E)

Institute of Pathology, University of Heidelberg, Germany.

Michael Hoffmeister (M)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Eric T P Keulen (ETP)

Department of Internal Medicine and Gastroenterology, Zuyderland Medical Center, Sittard, The Netherlands.

Dieuwertje E Kok (DE)

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Janna L Koole (JL)

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, The Netherlands.

Katharina Kosma (K)

Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria.

Ewout A Kouwenhoven (EA)

Department of Surgery, Hospital Group Twente ZGT, Almelo, The Netherlands.

Gry Kvalheim (G)

BEVITAL, Bergen, Norway.

Christopher I Li (CI)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Peter Schirmacher (P)

Institute of Pathology, University of Heidelberg, Germany.

Petra Schrotz-King (P)

Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.

Marie C Singer (MC)

Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria.

Fränzel J B van Duijnhoven (FJB)

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Henk K van Halteren (HK)

Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes, The Netherlands.

Kathy Vickers (K)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

F Jeroen Vogelaar (FJ)

Department of Surgery, VieCuri Medical Center, Venlo, The Netherlands.

Christy A Warby (CA)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

Evertine Wesselink (E)

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Per M Ueland (PM)

BEVITAL, Bergen, Norway.

Alexis B Ulrich (AB)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany.

Martin Schneider (M)

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany.

Nina Habermann (N)

Genome Biology, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Ellen Kampman (E)

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Matty P Weijenberg (MP)

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, The Netherlands.

Andrea Gsur (A)

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria.

Cornelia M Ulrich (CM)

Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

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