Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer
Zgaga L, Theodoratou E, Farrington SM, Din FV, Ooi LY, Glodzik D, Johnston S, Tenesa A, Campbell H, Dunlop MG
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 115 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Cancer Research UK
- Gobierno
- Medical Research Council
- Gobierno
- Chief Scientist Office
- Subvenciones
- Cancer Research UK (C26031/A11378); Cancer Research UK (C348/A12076); Cancer Research UK (12076); Medical Research Council (MR/K018647/1); Cancer Research UK (13154); Cancer Research UK (11378)
Según 3 financiadores declarados.
Publicación
- Publicado
- 2014-07-08 · J Clin Oncol · vol. 32 · número 23 · págs. 2430–2439
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 148 citas · más que el 99% de estudios similares · 11.3× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 42 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Vitamin D Research Studies · Colorectal Cancer Treatments and Studies · Nutritional Studies and Diet
- Palabras clave
- DØ, 25-hydroxyvitamin D, colorectal cancer, survival outcomes, vitamin D receptor gene, VDR polymorphisms, gene-environment interaction, stage II colorectal cancer, mortality, prognostic factors, vitamin D supplementation
- MeSH
- humans, colorectal neoplasms, vitamin d, receptors, calcitriol, neoplasm staging, risk factors, case-control studies, prospective studies, genotype, polymorphism, genetic, middle aged, scotland, female, male
10 autores
- Lina Zgaga🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Evropi Τheodoratou🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Susan Mary Farrington🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; Edinburgh Cancer Research; University of Edinburgh
- Farhat V N Din🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; Edinburgh Cancer Research; University of Edinburgh
- Li Yin Ooi🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Dominik Głodzik🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Susan S. Johnston🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Albert Tenesa🇬🇧🇮🇪Roslin Institute; Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Harry Campbell🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; University of Edinburgh
- Malcolm G. Dunlop🇮🇪🇬🇧Trinity College Dublin; Western General Hospital; Glasgow Royal Infirmary; Edinburgh Cancer Research; University of Edinburgh
Resumen
El texto original del estudio, en el idioma en que se publicó.
Purpose
We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.
Patients and methods
We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype-25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).
Results
We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).
Conclusion
In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.
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