McCullough ML, et al. - Researchers explored the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and colorectal cancer risk. In women, a statistically significant, substantially lower colorectal cancer risk was observed in relation to higher circulating 25(OH)D, while men exhibited a non-statistically significant lower risk in relation to higher circulating 25(OH)D. Optimal 25(OH)D concentrations for colorectal cancer risk reduction (75-100 nmol/L) appeared higher than current Institute of Medicine recommendations.

Methods

• From 17 cohorts, participant-level data was pooled, including 5,706 colorectal cancer cases and 7,107 controls with a wide range of circulating 25(OH)D concentrations.
• 25(OH)D was newly measured for 30.1% of participants.
• To allow estimating risk by absolute concentrations, previously measured 25(OH)D was calibrated to the same assay.
• They used conditional logistic regression and pooled using random effects models to calculate study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations.

Results

• They found that vs the lower range of sufficiency for bone health (50 – <62.5 nmol/L), deficient 25(OH)D ( < 30 nmol/L) was related to 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75 – <87.5 and 87.5 – <100 nmol/L) was related to 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively.
• No decline or no statistically significant reduction in risk was observed at 25(OH)D of 100 nmol/L or greater (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants).
• They observed that adjusting for body mass index, physical activity, or other risk factors had a minimal influence on associations.
• For each 25 nmol/L increment in circulating 25(OH)D, they observed 19% reduction in colorectal cancer risk in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% reduction in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided P_{heterogeneity} by sex = .008).
• Data revealed inverse associations in all subgroups, including colorectal subsite, geographic region, and season of blood collection.