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Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status
  1. Mingyang Song1,2,
  2. Reiko Nishihara1,3,
  3. Molin Wang2,
  4. Andrew T Chan4,5,
  5. Zhi Rong Qian3,
  6. Kentaro Inamura3,6,
  7. Xuehong Zhang5,
  8. Kimmie Ng3,
  9. Sun A Kim3,
  10. Kosuke Mima3,
  11. Yasutaka Sukawa3,
  12. Katsuhiko Nosho7,
  13. Charles S Fuchs3,5,
  14. Edward L Giovannucci1,2,5,
  15. Kana Wu1,
  16. Shuji Ogino2,3,5,8
  1. 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
  2. 2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
  4. 4Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
  6. 6Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  7. 7Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
  8. 8Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Shuji Ogino, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Ave, Room M422, Boston, MA 02215, USA; shuji_ogino{at}dfci.harvard.edu

Abstract

Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25-dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response.

Design We designed a nested case–control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses’ Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25(OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype.

Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend<0.001), but not risk of tumour with lower-level reaction (p for trend>0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006).

Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour–host interaction.

  • COLORECTAL CANCER
  • EPIDEMIOLOGY
  • NUTRITION
  • IMMUNOLOGY
  • IMMUNOTHERAPY

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