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The Impact of Vitamin D Pathway Genetic Variation and Circulating 25-Hydroxyvitamin D on Cancer Outcome: Systematic Review and Meta-Analysis

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Original languageEnglish
JournalBritish Journal of Cancer
Early online date16 Mar 2017
Publication statusE-pub ahead of print - 16 Mar 2017


Vitamin D has been linked with improved cancer outcome. This systematic review and meta-analysis investigates the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration.
A systematic review and meta-analysis of papers until November 2016 on PubMed, EMBASE and Web of Science pertaining to association between circulating vitamin D level, functionally relevant vitamin D receptor genetic variants and variants within vitamin D pathway genes and cancer survival or disease progression was performed.
A total of 44,165 cases from 64 studies were included in meta-analyses. Higher 25OHD was associated with better overall survival (hazard ratio (HR=0.74, 95%CI:0.66-0.82) and progression-free survival (HR=0.84, 95%CI:0.77-0.91). The rs1544410 (BsmI) variant was associated with overall survival (HR=1.40, 95%CI:1.05-1.75) and rs7975232 (ApaI) with progression-free survival (HR=1.29, 95%CI:1.02-1.56). The rs2228570 (FokI) variant was associated with overall survival in lung cancer patients (HR=1.29, 95%CI:1.0-1.57), with a suggestive association across all cancers (HR=1.26, 95%CI:0.96-1.56).
Higher 25OHD concentration is associated with better cancer outcome and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. This analysis provides powerful background rationale to instigate clinical trials to investigate the potential beneficial effect of vitamin D in the context of stratification by genotype

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