Prediagnostic 25-hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in western european populations

Veronika Fedirko, Elio Riboli, Anne Tjønneland, Pietro Ferrari, Anja Olsen, H. Bas Bueno-de-Mesquita, Fränzel J B Van Duijnhoven, Teresa Norat, Eugène H J M Jansen, Christina C. Dahm, Kim Overvad, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Antoine Racine, Annekatrin Lukanova, Birgit Teucher, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Vassiliki BenetouDimitrios Trichopoulos, Sara Grioni, Paolo Vineis, Salvatore Panico, Domenico Palli, Rosario Tumino, Peter D. Siersema, Petra H. Peeters, Guri Skeie, Magritt Brustad, Maria Dolores Chirlaque, Aurelio Barricarte, Jose Ramón Quirós, Maria José Sánchez, Miren Dorronsoro, Catalina Bonet, Richard Palmqvist, Göran Hallmans, Timothy J. Key, Francesca Crowe, Kay Tee Khaw, Nick Wareham, Isabelle Romieu, James McKay, Petra A. Wark, Dora Romaguera, Mazda Jenab

    Research output: Contribution to journalArticlepeer-review

    120 Citations (Scopus)


    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 onmortality 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.

    Original languageEnglish
    Pages (from-to)582-593
    Number of pages12
    JournalCancer Epidemiology Biomarkers and Prevention
    Issue number4
    Early online date25 Jan 2012
    Publication statusPublished - Apr 2012

    ASJC Scopus subject areas

    • Epidemiology
    • Oncology


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