TY - JOUR
T1 - Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality
AU - Wesselink, Evertine
AU - Kok, Dieuwertje E.
AU - Bours, Martijn J. L.
AU - de Wilt, Johannes H. W.
AU - van Baar, Harm
AU - van Zutphen, Moniek
AU - Geijsen, Anne M. J. R.
AU - Keulen, Eric T. P.
AU - Hansson, Bibi M. E.
AU - van den Ouweland, Jody
AU - Witkamp, Renger F.
AU - Weijenberg, Matty P.
AU - Kampman, Ellen
AU - van Duijnhoven, Franzel J. B.
N1 - Funding Information:
The COLON study was supported by Wereld Kanker Onderzoek Fonds and World Cancer Research Fund International grant 2014/1179 (to EK); Alpe d’Huzes/Dutch Cancer Society grants UM 2012-5653 (to MPW), UW 2013-5927 (to FJBvD), and UW 2015-7946 (to FJBvD); ERA-NET on Translational Cancer Research (TRANSCAN:Dutch Cancer Society) grants UW 2013-6397 (to EK) and UW 2014-6877 (to EK); and the Netherlands Organization for Health Research and Development. The EnCoRe study was supported by Stichting Alpe d’HuZes within the research program “Leven met kanker” of the Dutch Cancer Society grants UM 2010-4867 (to MPW) and UM 2012-5653 and by Kankeronderzoekfonds Limburg as part of Health Foundation Limburg grant 00005739 (to MPW).
Publisher Copyright:
Copyright © The Author(s) 2020.
PY - 2020/5
Y1 - 2020/5
N2 - Background: Higher concentrations of 25-hydroxyvitamin D-3[25(OH)D-3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism.Objectives: We aimed to investigate 25(OH)D-3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality.Methods: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D-3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D-3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another.Results: Serum 25(OH)D-3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D-3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 (vs.) (Q1): 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. (Q1): 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D-3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (>= 50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (Conclusions: Our findings suggest that the presence of an adequate status of 25(OH)D-3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings.
AB - Background: Higher concentrations of 25-hydroxyvitamin D-3[25(OH)D-3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism.Objectives: We aimed to investigate 25(OH)D-3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality.Methods: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D-3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D-3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another.Results: Serum 25(OH)D-3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D-3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 (vs.) (Q1): 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. (Q1): 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D-3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (>= 50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (Conclusions: Our findings suggest that the presence of an adequate status of 25(OH)D-3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings.
KW - colorectal cancer patients
KW - 25(OH)D-3
KW - interactions
KW - magnesium
KW - calcium
KW - recurrence
KW - all-cause mortality
KW - 25-HYDROXYVITAMIN D
KW - SURVIVAL
KW - HEALTH
KW - METABOLISM
KW - METASTASES
KW - PREVENTION
KW - PROTEIN
KW - TRIAL
U2 - 10.1093/ajcn/nqaa049
DO - 10.1093/ajcn/nqaa049
M3 - Article
C2 - 32190892
SN - 0002-9165
VL - 111
SP - 1007
EP - 1017
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 5
ER -