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 journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)98-107
Number of pages10
JournalEuropean Journal of Cancer
Volume103
DOIs
Publication statusPublished - 2018 Nov 1
Externally publishedYes

Fingerprint

Vitamin D
Colorectal Neoplasms
Survival
Confidence Intervals
Cyclooxygenase 2
Mortality
Life Style
Neoplasms
Tumor-Infiltrating Lymphocytes
Microsatellite Instability
CpG Islands
Health
Rectal Neoplasms
Proportional Hazards Models
Colonic Neoplasms
Methylation
Nurses
Diet
Carcinoma
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour. / Hamada, Tsuyoshi; Liu, Li; Nowak, Jonathan A.; Mima, Kosuke; Cao, Yin; Ng, Kimmie; Twombly, Tyler S.; Song, Mingyang; Jung, Seungyoun; Dou, Ruoxu; Masugi, Yohei; Kosumi, Keisuke; Shi, Yan; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Keum, Na Na; Wu, Kana; Nosho, Katsuhiko; Inamura, Kentaro; Meyerhardt, Jeffrey A.; Nevo, Daniel; Wang, Molin; Giannakis, Marios; Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.; Nishihara, Reiko; Zhang, Xuehong; Ogino, Shuji.

In: European Journal of Cancer, Vol. 103, 01.11.2018, p. 98-107.

Research output: Contribution to journalArticle

Hamada, T, Liu, L, Nowak, JA, Mima, K, Cao, Y, Ng, K, Twombly, TS, Song, M, Jung, S, Dou, R, Masugi, Y, Kosumi, K, Shi, Y, da Silva, A, Gu, M, Li, W, Keum, NN, Wu, K, Nosho, K, Inamura, K, Meyerhardt, JA, Nevo, D, Wang, M, Giannakis, M, Chan, AT, Giovannucci, EL, Fuchs, CS, Nishihara, R, Zhang, X & Ogino, S 2018, 'Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour', European Journal of Cancer, vol. 103, pp. 98-107. https://doi.org/10.1016/j.ejca.2018.07.130
Hamada, Tsuyoshi ; Liu, Li ; Nowak, Jonathan A. ; Mima, Kosuke ; Cao, Yin ; Ng, Kimmie ; Twombly, Tyler S. ; Song, Mingyang ; Jung, Seungyoun ; Dou, Ruoxu ; Masugi, Yohei ; Kosumi, Keisuke ; Shi, Yan ; da Silva, Annacarolina ; Gu, Mancang ; Li, Wanwan ; Keum, Na Na ; Wu, Kana ; Nosho, Katsuhiko ; Inamura, Kentaro ; Meyerhardt, Jeffrey A. ; Nevo, Daniel ; Wang, Molin ; Giannakis, Marios ; Chan, Andrew T. ; Giovannucci, Edward L. ; Fuchs, Charles S. ; Nishihara, Reiko ; Zhang, Xuehong ; Ogino, Shuji. / Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour. In: European Journal of Cancer. 2018 ; Vol. 103. pp. 98-107.
@article{e4fcb4f3835d4f649b90256898d923cb,
title = "Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour",
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",
author = "Tsuyoshi Hamada and Li Liu and Nowak, {Jonathan A.} and Kosuke Mima and Yin Cao and Kimmie Ng and Twombly, {Tyler S.} and Mingyang Song and Seungyoun Jung and Ruoxu Dou and Yohei Masugi and Keisuke Kosumi and Yan Shi and {da Silva}, Annacarolina and Mancang Gu and Wanwan Li and Keum, {Na Na} and Kana Wu and Katsuhiko Nosho and Kentaro Inamura and Meyerhardt, {Jeffrey A.} and Daniel Nevo and Molin Wang and Marios Giannakis and Chan, {Andrew T.} and Giovannucci, {Edward L.} and Fuchs, {Charles S.} and Reiko Nishihara and Xuehong Zhang and Shuji Ogino",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.ejca.2018.07.130",
language = "English",
volume = "103",
pages = "98--107",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",

}

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

PY - 2018/11/1

Y1 - 2018/11/1

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

UR - http://www.scopus.com/inward/record.url?scp=85053203682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053203682&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2018.07.130

DO - 10.1016/j.ejca.2018.07.130

M3 - Article

C2 - 30219720

AN - SCOPUS:85053203682

VL - 103

SP - 98

EP - 107

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -