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

ABSTRACT: 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.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.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.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.

SUBMITTER: Gray RT

PROVIDER: S-EPMC5518863 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Gray Ronan T RT Loughrey Maurice B MB Bankhead Peter P Cardwell Chris R CR McQuaid Stephen S O'Neill Roisin F RF Arthur Kenneth K Bingham Victoria V McGready Claire C Gavin Anna T AT James Jacqueline A JA Hamilton Peter W PW Salto-Tellez Manuel M Murray Liam J LJ Coleman Helen G HG

British journal of cancer 20170518 12

<h4>Background</h4>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.<h4>Methods</h4>The cohort consisted of 74 ...[more]

PMID: 28524155

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Project description:Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level.All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments.A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiagnostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72-0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74-0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55-0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64-0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality.In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.

Project description:BackgroundStatins have shown both protective and adverse associations with neuropsychiatric outcomes. We aimed to examine the possible associations between statins and suicidality, depression, anxiety, and seizures.MethodsUsing Swedish national registers, we linked data on dispensed statin prescriptions with data on unplanned (emergency) hospital visits or specialised outpatient care for four neuropsychiatric outcomes: suicidal behaviour (including deaths from suicide), depressive disorders, anxiety disorders, and seizures. We included all individuals in the registries who were dispensed statins and who were aged 15 years or older between Jan 1, 2006, and Dec 31, 2013. We applied a within-individual design using stratified Cox proportional hazards regression to compare the incidence of the defined outcomes during periods on statins and periods off statins within each individual, thus adjusting for time-invariant confounders. Non-specific effects of treatment were tested by investigating these outcomes in relation to thiazide diuretic use and antihistamine use in the same cohort.FindingsThe statin-users cohort comprised 1 149 384 individuals, of whom 1 015 949 (88·4%) were aged 50 years or older, 625 616 (54·4%) were male, and 523 768 (45·6%) were female. The study period consisted of 2 053 310 non-treatment periods and 2 997 545 treatment periods, and 957 216 (83·3%) individuals had a medication status change (from on statins to off statins, or vice versa). Suicide outcomes were found in 6372 (0·6%) individuals, depressive disorders in 23 745 (2·1%), anxiety disorders in 30 100 (2·6%), and seizures in 28 844 (2·5%). There were no clear associations between periods of statin treatment and suicidal behaviour or deaths from suicide (hazard ratio 0·99 [95% CI 0·90-1·08]), anxiety disorders (0·99 [0·95-1·02]), or seizures (1·00 [0·97-1·04]). Statins were associated with reduced hazards of depressive disorders (0·91 [0·87-0·94]), which remained after adjustment for concurrent antidepressant use (0·91 [0·88-0·94]). Hazard ratios for depressive disorders were 0·61 (0·38-1·00; n=14 718) with thiazide diuretic use and 0·84 (0·67-1·06; n=23 715) with antihistamine use.InterpretationStatin use is not associated with suicidality, anxiety disorders, or seizures. Whether the observed association between statin use and reduced diagnoses of clinical depression is confounded by non-specific benefits related to being prescribed medication needs further research.FundingWellcome Trust, Swedish Research Council, National Institute for Health Research (NIHR) Research Professorship, NIHR Oxford Health Biomedical Research Centre, American Foundation for Suicide Prevention, Karolinska Institutet.

Dataset Information

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

Publications

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

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