title: Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression.
abstract: BACKGROUND
  Despite accumulating evidence for the preventive effect of vitamin D on colorectal carcinogenesis, its precise mechanisms remain unclear. We hypothesized that vitamin D was associated with a lower risk of colorectal cancer with high-level vitamin D receptor (VDR) expression, but not with risk of tumor with low-level VDR expression.
  
  
  METHODS
  Among 140,418 participants followed from 1986 through 2008 in the Nurses' Health Study and the Health Professionals' Follow-up Study, we identified 1,059 incident colorectal cancer cases with tumor molecular data. The predicted 25-hydroxyvitamin D [25(OH)D] score was developed using the known determinants of plasma 25(OH)D. We estimated the HR for cancer subtypes using the duplication method Cox proportional hazards model.
  
  
  RESULTS
  A higher predicted 25(OH)D score was associated with a lower risk of colorectal cancer irrespective of VDR expression level (P(heterogeneity) for subtypes = 0.75). Multivariate HRs (95% confidence intervals) comparing the highest with the lowest quintile of predicted 25(OH)D scores were 0.48 (0.30-0.78) for VDR-negative tumor and 0.56 (0.42-0.75) for VDR-positive tumor. Similarly, the significant inverse associations of the predicted 25(OH)D score with colorectal cancer risk did not significantly differ by KRAS, BRAF, or PIK3CA status (P(heterogeneity) for subtypes ≥ 0.22).
  
  
  CONCLUSIONS
  A higher predicted vitamin D score was significantly associated with a lower colorectal cancer risk, regardless of VDR status and other molecular features examined.
  
  
  CONCLUSIONS
  The preventive effect of vitamin D on colorectal carcinogenesis may not totally depend on tumor factors. Host factors (such as local and systemic immunity) may need to be considered.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and.
authors.forename: Seungyoun
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Mai
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bertrand
authors.affiliation: Epidemiology.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Fitzgerald
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland; and.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Sun A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Epidemiology, Biostatistics, and.
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Epidemiology, Nutrition, Harvard School of Public Health, Boston, Massachusetts;
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smith-Warner
authors.affiliation: Nutrition, Harvard School of Public Health, Boston, Massachusetts;
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School;
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and Epidemiology, Nutrition, Harvard School of Public Health, Boston, Massachusetts;
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.affiliation: Channing Division of Network Medicine, Department of Medicine and Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of Epidemiology, rnishiha@hsph.harvard.edu shuji_ogino@dfci.harvard.edu.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of Nutrition, Harvard School of Public Health, Boston, Massachusetts; rnishiha@hsph.harvard.edu shuji_ogino@dfci.harvard.edu.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000032:analysis / Q000096:biosynthesis*; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D