Pre-diagnostic 25-Hydroxyvitamin D, VDR and CASR Polymorphisms, and Survival in Patients with Colorectal Cancer in Western European Populations
A partir des données de la cohorte européenne EPIC incluant 1 202 participants, cette étude prospective évalue l'association entre le niveau sanguin de calcifédiol (vitamine D) mesuré avant le diagnostic d'un cancer colorectal, des polymorphismes des gènes VDR et CASR, et la survie des patients
Background: Individuals with higher blood 25-hydroxy-vitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown. Methods: The association between pre-diagnostic 25(OH)D levels and CRC-specific (N=444) and overall mortality (N=541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992-2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle and metabolic effect modifiers were also investigated. Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend=0.04) and overall mortality (Ptrend=0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95%CI: 0.50-0.93) for CRC-specific and 0.67 (95%CI: 0.50-0.88) for overall mortality, compared to the lowest quintile. Except for a possible interaction by pre-diagnostic dietary calcium intake (Pinteraction=0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival. Conclusions: High pre-diagnostic 25(OH)D levels are associated with improved survival of patients with CRC. Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients.