Prediagnostic 25-hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in western European ppulations.
Fedirko V., Riboli E., Tjønneland A., Ferrari P., Olsen A., Bueno-de-Mesquita HB., van Duijnhoven FJ., Norat T., Jansen EH., Dahm CC., Overvad K., Boutron-Ruault MC., Clavel-Chapelon F., Racine A., Lukanova A., Teucher B., Boeing H., Aleksandrova K., Trichopoulou A., Benetou V., Trichopoulos D., Grioni S., Vineis P., Panico S., Palli D., Tumino R., Siersema PD., Peeters PH., Skeie G., Brustad M., Chirlaque MD., Barricarte A., Ramón Quirós J., Sánchez MJ., Dorronsoro M., Bonet C., Palmqvist R., Hallmans G., Key TJ., Crowe F., Khaw KT., Wareham N., Romieu I., McKay J., Wark PA., Romaguera D., Jenab M.
BACKGROUND: Individuals with higher blood 25-hydroxyvitamin 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 prediagnostic 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 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% 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 (P(trend) = 0.04) and overall mortality (P(trend) = 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 mortality and 0.67 (95% CI: 0.50-0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (P(interaction) = 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 prediagnostic 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.