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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85053203682&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.07.130
DO - 10.1016/j.ejca.2018.07.130
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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 -
