Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 6;116(12):1652-1659.
doi: 10.1038/bjc.2017.139. Epub 2017 May 18.

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

Ronan T Gray  1 , Maurice B Loughrey  2   3 , Peter Bankhead  2 , Chris R Cardwell  1 , Stephen McQuaid  2   4 , Roisin F O'Neill  1 , Kenneth Arthur  2 , Victoria Bingham  2 , Claire McGready  2 , Anna T Gavin  5 , Jacqueline A James  2   3   4 , Peter W Hamilton  2 , Manuel Salto-Tellez  2   3 , Liam J Murray  1 , Helen G Coleman  1
Affiliations

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

Ronan T Gray et al. Br J Cancer. .

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.

PubMed Disclaimer

Conflict of interest statement

PWH is the Founder and Director in PathXL Ltd. MS-T is a senior advisor to PathXL. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Selection of stage II and III colon cancer (adenocarcinoma) patients and samples. ICD=International Classification of Disease; NIB=Northern Ireland Biobank.
Figure 2
Figure 2
p53 immunohistochemistry in colon cancer tissue microarrays and associated markup for digital immunoscoring using QuPath image analysis software. Detected cells are colour-coded according to their classification: green=non-tumour; blue=negatively staining tumour; yellow=weakly staining tumour; orange=moderately staining tumour; red=strongly staining tumour. (A) Original core from a tumour demonstrating aberrant negative p53 immunostaining. (B) Original core from a tumour deomonstrating non-extreme (normal) p53 immunostaining. (C) Original core from a tumour demonstrating aberrant positive p53 immunostaining. (D) QuPath cellular markup in the aberrant negative p53 core. (E) QuPath cellular markup in the non-extreme (normal) p53 core. (F) QuPath cellular markup in the aberrant positive p53 core.
See this image and copyright information in PMC

References

    1. Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP (2014) Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol 15: e461–e468. - PMC - PubMed
    1. Bardou M, Barkun A, Martel M (2010) Effect of statin therapy on colorectal cancer. Gut 59: 1572–1585. - PubMed
    1. Bengtsson E, Nerjovaj P, Wangefjord S, Nodin B, Eberhard J, Uhlén M, Borgquist S, Jirström K, Uhlen M, Borgquist S, Jirstrom K (2014) HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome. Diagn Pathol 9: 78. - PMC - PubMed
    1. Bjarnadottir O, Romero Q, Bendahl P-O, Jirström K, Rydén L, Loman N, Uhlén M, Johannesson H, Rose C, Grabau D, Borgquist S (2013) Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial. Breast Cancer Res Treat 138: 499–508. - PubMed
    1. Borgquist S, Jögi A, Pontén F, Rydén L, Brennan DJ, Jirström K (2008) Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer. Breast Cancer Res 10: R79. - PMC - PubMed

MeSH terms

Substances