Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour

Eur J Cancer. 2018 Nov:103:98-107. doi: 10.1016/j.ejca.2018.07.130. Epub 2018 Sep 13.

Abstract

Background: High-level plasma 25-hydroxyvitamin D [25(OH)D] has been associated with lower colorectal cancer incidence and mortality. Considering evidence indicating immunomodulatory effects of vitamin D, we hypothesised that survival benefits from high systemic vitamin D level might be stronger for colorectal carcinoma with lower immune response to tumour.

Methods: Using 869 colon and rectal cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis 25(OH)D score [derived from diet and lifestyle variables to predict plasma 25(OH)D level] in strata of levels of histopathologic lymphocytic reaction. The Cox proportional hazards regression model was adjusted for potential confounders, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, PTGS2 (cyclooxygenase-2) expression and KRAS, BRAF and PIK3CA mutations.

Results: The association of postdiagnosis 25(OH)D score with colorectal cancer-specific mortality differed by levels of peritumoural lymphocytic reaction (pinteraction = 0.001). Multivariable-adjusted mortality hazard ratios for a quintile-unit increase of 25(OH)D score were 0.69 [95% confidence interval (CI), 0.54-0.89] in cases with negative/low peritumoural lymphocytic reaction, 1.08 (95% CI, 0.93-1.26) in cases with intermediate peritumoural reaction and 1.25 (95% CI, 0.75-2.09) in cases with high peritumoural reaction. The survival association of the 25(OH)D score did not significantly differ by Crohn's-like lymphoid reaction, intratumoural periglandular reaction or tumour-infiltrating lymphocytes.

Conclusions: The association between the 25(OH)D score and colorectal cancer survival is stronger for carcinomas with lower peritumoural lymphocytic reaction. Our results suggesting interactive effects of vitamin D and immune response may contribute to personalised dietary and lifestyle intervention strategies.

Keywords: Clinical outcome; Immunology; Molecular pathological epidemiology; Precision medicine; Tumour microenvironment.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Precision Medicine / methods
  • Prospective Studies
  • Survival Analysis
  • Tumor Microenvironment / drug effects*