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; NaNa Keum; Kana Wu; Katsuhiko Nosho; Kentaro Inamura; Jeffrey A Meyerhardt; Daniel Nevo; Molin Wang; Marios Giannakis; Andrew T Chan; Edward L Giovannucci; Charles S Fuchs; Reiko Nishihara; Xuehong Zhang; Shuji Ogino

doi:10.1016/j.ejca.2018.07.130

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.

Authors

Tsuyoshi Hamada¹, Li Liu², Jonathan A Nowak³, Kosuke Mima⁴, Yin Cao⁵, Kimmie Ng⁴, Tyler S Twombly¹, Mingyang Song⁶, Seungyoun Jung⁷, Ruoxu Dou⁴, Yohei Masugi¹, Keisuke Kosumi¹, Yan Shi⁸, Annacarolina da Silva¹, Mancang Gu⁹, Wanwan Li¹, NaNa Keum¹⁰, Kana Wu¹¹, Katsuhiko Nosho¹², Kentaro Inamura¹³, Jeffrey A Meyerhardt⁴, Daniel Nevo¹⁴, Molin Wang¹⁵, Marios Giannakis¹⁶, Andrew T Chan¹⁷, Edward L Giovannucci¹¹, Charles S Fuchs¹⁸, Reiko Nishihara¹⁹, Xuehong Zhang²⁰, Shuji Ogino²¹

Affiliations

¹ Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
² Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Hubei, PR China.
³ Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
⁸ Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Chinese PLA General Hospital, Beijing, PR China.
⁹ Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; College of Pharmacy, Zhejiang Chinese Medical University, Zhejiang, PR China.
¹⁰ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Food Science and Biotechnology, Dongguk University, Goyang, Republic of Korea.
¹¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹² Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
¹³ Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
¹⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁶ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁸ Yale Cancer Center, New Haven, CT, USA; Department of Medicine, Yale School of Medicine, New Haven, CT, USA; Smilow Cancer Hospital, New Haven, CT, USA.
¹⁹ Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁰ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: xuehong.zhang@channing.harvard.edu.
²¹ Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: shuji_ogino@dfci.harvard.edu.

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 (p_interaction = 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*

Abstract

Publication types

MeSH terms

Grants and funding