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Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1628-37. doi: 10.1158/1055-9965.EPI-14-0229. Epub 2014 Jun 11.

Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression.

Author information

1
Channing Division of Network Medicine, Department of Medicine and.
2
Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
3
Epidemiology.
4
Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland; and.
5
Epidemiology, Biostatistics, and.
6
Epidemiology, Nutrition, Harvard School of Public Health, Boston, Massachusetts;
7
Nutrition, Harvard School of Public Health, Boston, Massachusetts;
8
Channing Division of Network Medicine, Department of Medicine and Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of.
9
Channing Division of Network Medicine, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School;
10
Channing Division of Network Medicine, Department of Medicine and Epidemiology, Nutrition, Harvard School of Public Health, Boston, Massachusetts;
11
Channing Division of Network Medicine, Department of Medicine and Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
12
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.
13
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.

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.

IMPACT:

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.

PMID:
24920642
PMCID:
PMC4119536
DOI:
10.1158/1055-9965.EPI-14-0229
[Indexed for MEDLINE]
Free PMC Article

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