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

Tsuyoshi Hamada, Li Liu, Jonathan A. Nowak, Kosuke Mima, Yin Cao, Kimmie Ng, Tyler S. Twombly, Mingyang Song, Seungyoun Jung, Ruoxu Dou, Yohei Masugi, Keisuke Kosumi, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, Na Na Keum, Kana Wu, Katsuhiko Nosho, Kentaro InamuraJeffrey A. Meyerhardt, Daniel Nevo, Molin Wang, Marios Giannakis, Andrew T. Chan, Edward L. Giovannucci, Charles S. Fuchs, Reiko Nishihara, Xuehong Zhang, Shuji Ogino

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)98-107
Number of pages10
JournalEuropean Journal of Cancer
StatePublished - Nov 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Ltd


  • Clinical outcome
  • Immunology
  • Molecular pathological epidemiology
  • Precision medicine
  • Tumour microenvironment


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