Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 1;28(6):1359-1367.
doi: 10.1093/annonc/mdx109.

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance)

M A Fuchs  1 , C Yuan  1   2 , K Sato  1 , D Niedzwiecki  3 , X Ye  3 , L B Saltz  4 , R J Mayer  1 , R B Mowat  5 , R Whittom  6 , A Hantel  7 , A Benson  8 , D Atienza  9 , M Messino  10 , H Kindler  11 , A Venook  12 , F Innocenti  13 , R S Warren  12 , M M Bertagnolli  1   14 , S Ogino  1   2   15 , E L Giovannucci  2   16   17 , E Horvath  18 , J A Meyerhardt  1 , K Ng  1
Affiliations

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance)

M A Fuchs et al. Ann Oncol. .

Abstract

Background: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown.

Patients and methods: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards.

Results: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status.

Conclusion: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted.

Clinicaltrials.gov identifier: NCT00003835.

Keywords: colorectal neoplasm; prospective studies; survival analysis; vitamin D.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Derivation of the study cohort. Q1, questionnaire 1 (midway through adjuvant therapy); Q2, questionnaire 2 (6 months after completion of adjuvant therapy); caloric intake exclusion, <600 or > 4200 calories/day for men and <500 or > 3500 calories/day for women.
Figure 2.
Figure 2.
(A) Disease-free survival according to tertile of post-diagnosis predicted 25(OH)D levels. (B) Recurrence-free survival according to tertile of post-diagnosis predicted 25(OH)D levels. (C) Overall survival according to tertile of post-diagnosis predicted 25(OH)D levels. 25(OH)D, 25-hydroxyvitamin D.
Figure 3.
Figure 3.
Adjusted hazard ratios (HR) and 95% confidence intervals (CI) comparing highest to lowest tertiles of predicted 25(OH)D level for disease-free survival across strata of predictors of patient outcome and tumor molecular features. FU/LV, 5-fluorouracil and leucovorin; IFL, irinotecan; MET, metabolic equivalent; MSI, microsatellite instability; MSS, microsatellite stable.
See this image and copyright information in PMC

References

    1. Larriba MJ, Ordonez-Moran P, Chicote I. et al. Vitamin D receptor deficiency enhances Wnt/beta-catenin signaling and tumor burden in colon cancer. PLoS One 2011; 6: e23524.. - PMC - PubMed
    1. Zheng W, Wong KE, Zhang Z. et al. Inactivation of the vitamin D receptor in APC(min/+) mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. Int J Cancer 2012; 130: 10–19. - PMC - PubMed
    1. Morales-Oyarvide V, Meyerhardt JA, Ng K.. Vitamin D and physical activity in patients with colorectal cancer: epidemiological evidence and therapeutic implications. Cancer J 2016; 22: 223–231. - PMC - PubMed
    1. Saltz LB, Niedzwiecki D, Hollis D. et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. JCO 2007; 25: 3456–3461. - PubMed
    1. Meyerhardt JA, Sato K, Niedzwiecki D. et al. Dietary glycemic load and cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Natl Cancer Inst 2012; 104: 1702–1711. - PMC - PubMed

Associated data