Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer in the Nurses' Health Study.

Total circulating 25-hydroxyvitamin D [25(OH)D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH)D, which is influenced by levels of vitamin D binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH)D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989-1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH)D levels based on total 25(OH)D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH)D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25(OH)D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33-0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65-1.47), free 25(OH)D (OR, 0.71; 95% CI, 0.46-1.10), or bioavailable 25(OH)D (OR, 0.92; 95% CI, 0.60-1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH)D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. Cancer Prev Res; 9(8); 664-72. ©2016 AACR. ©2016 American Association for Cancer Research.