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

doi:10.1038/bjc.2017.139

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 journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	1652-1659
Number of pages	8
Journal	British Journal of Cancer
Volume	116
Issue number	12
Early online date	6 Jun 2017
DOIs	https://doi.org/10.1038/bjc.2017.139
Publication status	Published - 6 Jun 2017

Keywords / Materials (for Non-textual outputs)

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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10.1038/bjc.2017.139

bjc2017139
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Peter Bankhead
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Gray, R. T., Loughrey, M. B., Bankhead, P., Cardwell, C. R., McQuaid, S., O'Neill, R. F., Arthur, K., Bingham, V., McGready, C., Gavin, A. T., James, J. A., Hamilton, P. W., Salto-Tellez, M., Murray, L. J., & Coleman, H. G. (2017). Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study. British Journal of Cancer, 116(12), 1652-1659. https://doi.org/10.1038/bjc.2017.139

@article{bc779151fca942ceb4205d7a1d9e32df,

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

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.",

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",

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

year = "2017",

month = jun,

day = "6",

doi = "10.1038/bjc.2017.139",

language = "English",

volume = "116",

pages = "1652--1659",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "12",

}

Gray, RT, Loughrey, MB, Bankhead, P, Cardwell, CR, McQuaid, S, O'Neill, RF, Arthur, K, Bingham, V, McGready, C, Gavin, AT, James, JA, Hamilton, PW, Salto-Tellez, M, Murray, LJ & Coleman, HG 2017, 'Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study', British Journal of Cancer, vol. 116, no. 12, pp. 1652-1659. https://doi.org/10.1038/bjc.2017.139

TY - JOUR

T1 - Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study

AU - Gray, Ronan T

AU - Loughrey, Maurice B

AU - Bankhead, Peter

AU - Cardwell, Chris R

AU - McQuaid, Stephen

AU - O'Neill, Roisin F

AU - Arthur, Kenneth

AU - Bingham, Victoria

AU - McGready, Claire

AU - Gavin, Anna T

AU - James, Jacqueline A

AU - Hamilton, Peter W

AU - Salto-Tellez, Manuel

AU - Murray, Liam J

AU - Coleman, Helen G

PY - 2017/6/6

Y1 - 2017/6/6

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor/analysis

KW - Cohort Studies

KW - Colonic Neoplasms/chemistry

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl CoA Reductases/analysis

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Male

KW - Metabolic Networks and Pathways

KW - Mevalonic Acid/metabolism

KW - Middle Aged

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Survival Rate

KW - Tumor Suppressor Protein p53/analysis

U2 - 10.1038/bjc.2017.139

DO - 10.1038/bjc.2017.139

M3 - Article

C2 - 28524155

SN - 0007-0920

VL - 116

SP - 1652

EP - 1659

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 12

ER -

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

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Peter Bankhead

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