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Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer : Findings from CALGB/SWOG 80702 (Alliance)

Wang, Qiao-Li LU orcid ; Ma, Chao ; Yuan, Chen ; Shi, Qian ; Wolpin, Brian M ; Zhang, Yin ; Fuchs, Charles S ; Meyer, Jeffrey ; Zemla, Tyler and Cheng, En , et al. (2023) In Clinical cancer research : an official journal of the American Association for Cancer Research 29(14). p.2621-2630
Abstract

PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.

EXPERIMENTAL DESIGN: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2).

RESULTS: Vitamin... (More)

PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.

EXPERIMENTAL DESIGN: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2).

RESULTS: Vitamin D deficiency [25(OH)D <12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank<0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51-0.92) for DFS, 0.57 (0.40-0.80) for OS, and 0.71 (0.52-0.98) for TTR. A U-shaped dose-response pattern was observed for DFS and OS (both Pnonlinearity<0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events.

CONCLUSIONS: Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.

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publishing date
type
Contribution to journal
publication status
published
keywords
Humans, Interleukin-6, Vitamin D, Colonic Neoplasms, Vitamins, Disease-Free Survival, C-Reactive Protein
in
Clinical cancer research : an official journal of the American Association for Cancer Research
volume
29
issue
14
pages
2621 - 2630
publisher
American Association for Cancer Research Inc.
external identifiers
  • scopus:85164843217
  • pmid:37289007
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-23-0447
language
English
LU publication?
no
additional info
©2023 American Association for Cancer Research.
id
b5604065-6ab6-4076-9b08-39934b52f86d
date added to LUP
2025-05-12 17:09:31
date last changed
2025-07-08 09:52:46
@article{b5604065-6ab6-4076-9b08-39934b52f86d,
  abstract     = {{<p>PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.</p><p>EXPERIMENTAL DESIGN: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2).</p><p>RESULTS: Vitamin D deficiency [25(OH)D &lt;12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank&lt;0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51-0.92) for DFS, 0.57 (0.40-0.80) for OS, and 0.71 (0.52-0.98) for TTR. A U-shaped dose-response pattern was observed for DFS and OS (both Pnonlinearity&lt;0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events.</p><p>CONCLUSIONS: Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.</p>}},
  author       = {{Wang, Qiao-Li and Ma, Chao and Yuan, Chen and Shi, Qian and Wolpin, Brian M and Zhang, Yin and Fuchs, Charles S and Meyer, Jeffrey and Zemla, Tyler and Cheng, En and Kumthekar, Priya and Guthrie, Katherine A and Couture, Felix and Kuebler, Philip and Kumar, Pankaj and Tan, Benjamin and Krishnamurthi, Smitha and Goldberg, Richard M and Venook, Alan and Blanke, Charles and Shields, Anthony F and O'Reilly, Eileen M and Meyerhardt, Jeffrey A and Ng, Kimmie}},
  issn         = {{1078-0432}},
  keywords     = {{Humans; Interleukin-6; Vitamin D; Colonic Neoplasms; Vitamins; Disease-Free Survival; C-Reactive Protein}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{14}},
  pages        = {{2621--2630}},
  publisher    = {{American Association for Cancer Research Inc.}},
  series       = {{Clinical cancer research : an official journal of the American Association for Cancer Research}},
  title        = {{Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer : Findings from CALGB/SWOG 80702 (Alliance)}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-23-0447}},
  doi          = {{10.1158/1078-0432.CCR-23-0447}},
  volume       = {{29}},
  year         = {{2023}},
}