The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

Evertine Wesselink; Michiel Balvers; Martijn J. L. Bours; Johannes H. W. de Wilt; Renger F. Witkamp; Harm van Baar; Anne J. M. R. Geijsen; Henk van Halteren; Eric T. P. Keulen; Dieuwertje E. Kok; Ewout A. Kouwenhoven; Jody van den Ouweland; Moniek van Zutphen; Matty P. Weijenberg; Ellen Kampman; Fränzel J. B. van Duijnhoven

doi:10.1177/1756284820923922

The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

Evertine Wesselink, Michiel Balvers, Martijn J. L. Bours, Johannes H. W. de Wilt, Renger F. Witkamp, Harm van Baar, Anne J. M. R. Geijsen, Henk van Halteren, Eric T. P. Keulen, Dieuwertje E. Kok, Ewout A. Kouwenhoven, Jody van den Ouweland, Moniek van Zutphen, Matty P. Weijenberg, Ellen Kampman, Fränzel J. B. van Duijnhoven

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

Original language	English
Journal	Therapeutic Advances in Gastroenterology
Volume	13
DOIs	https://doi.org/10.1177/1756284820923922
Publication status	Published - 2020
Externally published	Yes

Funding

The authors thank the participants of the COLON study and the investigators at Wageningen University & Research and the co-workers from the following hospitals for their involvement in recruitment for the COLON study: Hospital Gelderse Vallei, Ede; Radboudumc, Nijmegen; Slingeland Hospital, Doetinchem,; Canisius Wilhelmina Hospital, Nijmegen; Rijnstate Hospital, Arnhem; Gelre Hospitals, Apeldoorn/Zutphen; Hospital Bernhoven, Uden; Isala, Zwolle; ZGT, Almelo; Martini Hospital, Groningen; Admiraal de Ruyter Hospital, Goes/Vlissingen. We also thank all participants of the EnCoRe study and the health professionals in the three hospitals involved in the recruitment of participants of the study: Maastricht University Medical Center, VieCuri Medical Center, and Zuyderland Medical Center. We additionally thank the MEMIC center for data and information management for facilitating the logistic processes and data management of our study. Furthermore, we thank the research dieticians and research assistant who are responsible for patient inclusion and follow-up, performing home visits, as well as data collection and processing. Finally, we thank BEVITAL, Bergen, Norway for analysing hsCRP in the COLON and EnCoRe studies. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Wereld Kanker Onderzoek Fonds, including funds from grant 2014/1179 as part of the World Cancer Research Fund International Regular Grant Programme; Alpe d’Huzes/Dutch Cancer Society (grant numbers UM 2012-5653, UW 2013-5927 and UW 2015-7946); and ERA-NET on Translational Cancer Research (TRANSCAN/Dutch Cancer Society: grant numbers UW2013-6397 and UW2014-6877). The EnCoRe study was supported by a grant from the Stichting Alpe d’HuZes within the research program ‘Leven met kanker’ of the Dutch Cancer Society (grant number UM-2010-4867) and by a grant from Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (grant number 00005739). The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Wereld Kanker Onderzoek Fonds, including funds from grant 2014/1179 as part of the World Cancer Research Fund International Regular Grant Programme; Alpe d’Huzes/Dutch Cancer Society (grant numbers UM 2012-5653, UW 2013-5927 and UW 2015-7946); and ERA-NET on Translational Cancer Research (TRANSCAN/Dutch Cancer Society: grant numbers UW2013-6397 and UW2014-6877). The EnCoRe study was supported by a grant from the Stichting Alpe d’HuZes within the research program ‘Leven met kanker’ of the Dutch Cancer Society (grant number UM-2010-4867) and by a grant from Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (grant number 00005739).

Funders	Funder number
Admiraal de Ruyter Hospital
COLON
Canisius Wilhelmina Hospital
ERA-NET on Translational Cancer Research
Slingeland Hospital
Stichting Alpe d’HuZes	00005739, UM-2010-4867
TRANSCAN	UW2013-6397, UW2014-6877
VieCuri Medical Center
Zuyderland Medical Center
Maastricht Universitair Medisch Centrum
KWF Kankerbestrijding	UM 2012-5653, UW 2013-5927, UW 2015-7946
Wereld Kanker Onderzoek Fonds	2014/1179

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Wesselink, E., Balvers, M., Bours, M. J. L., de Wilt, J. H. W., Witkamp, R. F., van Baar, H., Geijsen, A. J. M. R., van Halteren, H., Keulen, E. T. P., Kok, D. E., Kouwenhoven, E. A., van den Ouweland, J., van Zutphen, M., Weijenberg, M. P., Kampman, E., & van Duijnhoven, F. J. B. (2020). The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis. Therapeutic Advances in Gastroenterology, 13. https://doi.org/10.1177/1756284820923922

@article{9fb1fac2640d45d48f2ead60b9cb8426,

title = "The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis",

abstract = "Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.",

author = "Evertine Wesselink and Michiel Balvers and Bours, {Martijn J. L.} and {de Wilt}, {Johannes H. W.} and Witkamp, {Renger F.} and {van Baar}, Harm and Geijsen, {Anne J. M. R.} and {van Halteren}, Henk and Keulen, {Eric T. P.} and Kok, {Dieuwertje E.} and Kouwenhoven, {Ewout A.} and {van den Ouweland}, Jody and {van Zutphen}, Moniek and Weijenberg, {Matty P.} and Ellen Kampman and {van Duijnhoven}, {Fr{\"a}nzel J. B.}",

year = "2020",

doi = "10.1177/1756284820923922",

language = "English",

volume = "13",

journal = "Therapeutic Advances in Gastroenterology",

issn = "1756-283X",

publisher = "SAGE Publications Ltd",

}

Wesselink, E, Balvers, M, Bours, MJL, de Wilt, JHW, Witkamp, RF, van Baar, H, Geijsen, AJMR, van Halteren, H, Keulen, ETP, Kok, DE, Kouwenhoven, EA, van den Ouweland, J, van Zutphen, M, Weijenberg, MP, Kampman, E & van Duijnhoven, FJB 2020, 'The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis', Therapeutic Advances in Gastroenterology, vol. 13. https://doi.org/10.1177/1756284820923922

TY - JOUR

T1 - The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

AU - Wesselink, Evertine

AU - Balvers, Michiel

AU - Bours, Martijn J. L.

AU - de Wilt, Johannes H. W.

AU - Witkamp, Renger F.

AU - van Baar, Harm

AU - Geijsen, Anne J. M. R.

AU - van Halteren, Henk

AU - Keulen, Eric T. P.

AU - Kok, Dieuwertje E.

AU - Kouwenhoven, Ewout A.

AU - van den Ouweland, Jody

AU - van Zutphen, Moniek

AU - Weijenberg, Matty P.

AU - Kampman, Ellen

AU - van Duijnhoven, Fränzel J. B.

PY - 2020

Y1 - 2020

N2 - Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

AB - Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

UR - http://www.scopus.com/inward/record.url?scp=85085593158&partnerID=8YFLogxK

U2 - 10.1177/1756284820923922

DO - 10.1177/1756284820923922

M3 - Article

SN - 1756-283X

VL - 13

JO - Therapeutic Advances in Gastroenterology

JF - Therapeutic Advances in Gastroenterology

ER -

The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

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