Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study

Ronan T Gray, Maurice B Loughrey, Peter Bankhead, Chris R Cardwell, Stephen McQuaid, Roisin F O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T Gavin, Jacqueline A James, Peter W Hamilton, Manuel Salto-Tellez, Liam J Murray, Helen G Coleman

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed.

METHODS: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008. Statin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical expression of p53 and HMGCR in tissue microarrays and the presence of KRAS mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer-specific and overall survival.

RESULTS: Statin use was not associated with improved cancer-specific survival in this cohort (HR=0.91, 95% CI 0.64-1.28). Statin use was also not associated with improved survival when the analyses were stratified by tumour p53 (wild-type HR=1.31, 95% CI 0.67-2.56 vs aberrant HR=0.80, 95% CI 0.52-1.24), HMGCR (HMGCR-high HR=0.69, 95% CI 0.40-1.18 vs HMGCR-low HR=1.10, 95% CI 0.66-1.84), and KRAS (wild-type HR=0.73, 95% CI 0.44-1.19 vs mutant HR=1.21, 95% CI 0.70-2.21) status.

CONCLUSIONS: Statin use was not associated with improved survival either independently or when stratified by potential mevalonate pathway biomarkers in this population-based cohort of colon cancer patients.

Original languageEnglish
Pages (from-to)1652-1659
Number of pages8
JournalBritish Journal of Cancer
Volume116
Issue number12
Early online date6 Jun 2017
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/analysis
  • Cohort Studies
  • Colonic Neoplasms/chemistry
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases/analysis
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  • Male
  • Metabolic Networks and Pathways
  • Mevalonic Acid/metabolism
  • Middle Aged
  • Proto-Oncogene Proteins p21(ras)/genetics
  • Survival Rate
  • Tumor Suppressor Protein p53/analysis

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