Plasma 25-hydroxyvitamin D and risk of colorectal cancer after adjusting for inflammatory markers.

Despite the substantial epidemiologic evidence on the inverse association between circulating 25-hydroxyvitamin D [25(OH)D] and colorectal cancer, it remains controversial whether this relationship is causal or due to confounding by inflammation. We reevaluated the association between plasma 25(OH)D and colorectal cancer risk by additionally accounting for inflammatory markers in a prospective case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study (615 cases and 1,209 matched controls). Conditional logistic regression was used to estimate relative risk (RR) and 95% confidence interval (CI) of colorectal cancer in relation to quartiles of plasma 25(OH)D. Results were compared before and after adjusting for inflammatory markers in the multivariable model. Plasma 25(OH)D was associated with reduced risk of colorectal cancer (multivariable RR comparing extreme quartiles = 0.71; 95% CI, 0.52-0.97; Ptrend = 0.01). Additional adjustment for C-reactive protein, IL6, soluble tumor necrosis factor receptor 2, or a composite inflammatory score did not change the results [multivariable (including inflammatory score) RR = 0.72; 95% CI, 0.53-0.98; Ptrend = 0.02). Our findings suggest that confounding by inflammation, as reflected by circulating inflammatory markers, does not appear to account for the inverse association between plasma 25(OH)D and colorectal cancer.