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

Seungyoun Jung, Zhi Rong Qian, Mai Yamauchi, Kimberly A. Bertrand, Kathryn C. Fitzgerald, Kentaro Inamura, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Xuehong Zhang, Molin Wang, Stephanie A. Smith-Warner, Kana Wu, Charles S. Fuchs, Andrew T. Chan, Edward L. Giovannucci, Kimmie Ng, Eunyoung Cho, Shuji Ogino, Reiko Nishihara

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17 Citations (Scopus)

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 (Pheterogeneity 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.

Original languageEnglish
Pages (from-to)1628-1637
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number8
DOIs
Publication statusPublished - 2014 Aug

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Jung, S., Qian, Z. R., Yamauchi, M., Bertrand, K. A., Fitzgerald, K. C., Inamura, K., Kim, S. A., Mima, K., Sukawa, Y., Zhang, X., Wang, M., Smith-Warner, S. A., Wu, K., Fuchs, C. S., Chan, A. T., Giovannucci, E. L., Ng, K., Cho, E., Ogino, S., & Nishihara, R. (2014). Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression. Cancer Epidemiology Biomarkers and Prevention, 23(8), 1628-1637. https://doi.org/10.1158/1055-9965.EPI-14-0229