TY - JOUR
T1 - Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour
AU - Hamada, Tsuyoshi
AU - Liu, Li
AU - Nowak, Jonathan A.
AU - Mima, Kosuke
AU - Cao, Yin
AU - Ng, Kimmie
AU - Twombly, Tyler S.
AU - Song, Mingyang
AU - Jung, Seungyoun
AU - Dou, Ruoxu
AU - Masugi, Yohei
AU - Kosumi, Keisuke
AU - Shi, Yan
AU - da Silva, Annacarolina
AU - Gu, Mancang
AU - Li, Wanwan
AU - Keum, Na Na
AU - Wu, Kana
AU - Nosho, Katsuhiko
AU - Inamura, Kentaro
AU - Meyerhardt, Jeffrey A.
AU - Nevo, Daniel
AU - Wang, Molin
AU - Giannakis, Marios
AU - Chan, Andrew T.
AU - Giovannucci, Edward L.
AU - Fuchs, Charles S.
AU - Nishihara, Reiko
AU - Zhang, Xuehong
AU - Ogino, Shuji
N1 - Funding Information:
This work was supported by U.S. National Institutes of Health (NIH) grants ( P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003 to C.S.F.; R01 CA118553 to C.S.F.; R01 CA169141 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; R01 CA151993 to S.O.; R01 CA205406 to K.Ng; K07 CA190673 to R.N. and K07 CA188126 to X.Z.); by Nodal Award (2016-02) from the Dana-Farber Harvard Cancer Center (to S.O.) and by grants from the Project P Fund , The Friends of the Dana-Farber Cancer Institute , Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. This work was additionally supported by the Stand Up to Cancer (SU2C) Colorectal Cancer Dream Team Translational Research Grant ( SU2C-AACR-DT22-17 to M.Gi. and C.S.F.). The SU2C is a program of the Entertainment Industry Foundation, and research grants are administered by the American Association for Cancer Research, a scientific partner of SU2C. T.H. was supported by a fellowship grant from the Uehara Memorial Foundation and by a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research . L.L. was supported by a scholarship grant from Chinese Scholarship Council and a fellowship grant from Huazhong University of Science and Technology . K.M. was supported by a grant from Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japan Society for the Promotion of Science . K.K. was supported by grants from Overseas Research Fellowship ( JP2017-775 ) and Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers, from Japan Society for the Promotion of Science . R.D. was supported by a grant from National Natural Science Foundation of China ( 31601077 ). N.K. was supported by grants from the National Research Foundation of Korea ( NRF-2018R1C1B6008822 and NRF-2018R1A4A1022589 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.
Funding Information:
A.T.C. previously served as a consultant for Bayer Healthcare, Pfizer Inc. and Aralez Pharmaceuticals. This study was not funded by Bayer Healthcare, Pfizer Inc. or Aralez Pharmaceuticals. No other conflicts of interest exist. The other authors declare that they have no conflicts of interest.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - Clinical outcome
KW - Immunology
KW - Molecular pathological epidemiology
KW - Precision medicine
KW - Tumour microenvironment
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U2 - 10.1016/j.ejca.2018.07.130
DO - 10.1016/j.ejca.2018.07.130
M3 - Article
C2 - 30219720
AN - SCOPUS:85053203682
SN - 0959-8049
VL - 103
SP - 98
EP - 107
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
