Skip to main content
Top
Published in: Digestive Diseases and Sciences 7/2014

01-07-2014 | Original Article

Aspirin May Prevent Cholangiocarcinoma: A Case–Control Study from the United Kingdom

Authors: N. E. Burr, R. J. Talboys, S. Savva, A. Clark, M. Phillips, M. Metcalfe, A. Dennison, R. Robinson, M. P. Lewis, M. Rhodes, S. Rushbrook, A. R. Hart

Published in: Digestive Diseases and Sciences | Issue 7/2014

Login to get access

Abstract

Background

The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle.

Aims

To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma.

Methods

This epidemiological study had a case–control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI).

Results

In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22–0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11–1.42) or statins (OR 0.58; 95 % CI 0.28–1.19).

Conclusions

The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.
Literature
1.
go back to reference Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998 [Internet]. CA Cancer J Clin. 1998;48:6–29.PubMedCrossRef Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998 [Internet]. CA Cancer J Clin. 1998;48:6–29.PubMedCrossRef
2.
go back to reference Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document [Internet]. GUT. 2002;51:VI1–VI9.PubMedCentralPubMedCrossRef Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document [Internet]. GUT. 2002;51:VI1–VI9.PubMedCentralPubMedCrossRef
3.
go back to reference West J, Wood H, Logan RF, Quinn M, Aithal GP. Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer. 2006;94:1751–1758.PubMedCentralPubMedCrossRef West J, Wood H, Logan RF, Quinn M, Aithal GP. Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer. 2006;94:1751–1758.PubMedCentralPubMedCrossRef
4.
5.
go back to reference Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99:523–526.PubMedCrossRef Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99:523–526.PubMedCrossRef
6.
go back to reference Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis [Internet]. Ann Surg. 1991;213:21–25.PubMedCentralPubMedCrossRef Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis [Internet]. Ann Surg. 1991;213:21–25.PubMedCentralPubMedCrossRef
7.
go back to reference Bergquist A, Broomé U. Hepatobiliary and extra-hepatic malignancies in primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol. 2001;15:643–656.PubMedCrossRef Bergquist A, Broomé U. Hepatobiliary and extra-hepatic malignancies in primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol. 2001;15:643–656.PubMedCrossRef
8.
go back to reference Sorensen HT, Friis S, Olsen JH, et al. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology. 1998;28:921–925.PubMedCrossRef Sorensen HT, Friis S, Olsen JH, et al. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology. 1998;28:921–925.PubMedCrossRef
9.
go back to reference Shaib YH, El-Serag HB, Davila JA, Morgan R, McGlynn KA. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case–control study. Gastroenterology. 2005;128:620–626.PubMedCrossRef Shaib YH, El-Serag HB, Davila JA, Morgan R, McGlynn KA. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case–control study. Gastroenterology. 2005;128:620–626.PubMedCrossRef
10.
go back to reference Yamamoto S, Kubo S, Hai S, et al. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma [Internet]. Cancer Sci. 2004;95:592–595.PubMedCrossRef Yamamoto S, Kubo S, Hai S, et al. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma [Internet]. Cancer Sci. 2004;95:592–595.PubMedCrossRef
11.
go back to reference Shin HR, Lee CU, Park HJ, et al. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea [Internet]. Int J Epidemiol. 1996;25:933–940.PubMedCrossRef Shin HR, Lee CU, Park HJ, et al. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea [Internet]. Int J Epidemiol. 1996;25:933–940.PubMedCrossRef
12.
go back to reference Kubo S, Kinoshita H, Hirohashi K, Hamba H. Hepatolithiasis associated with cholangiocarcinoma [Internet]. World J Surg. 1995;19:637–641.PubMedCrossRef Kubo S, Kinoshita H, Hirohashi K, Hamba H. Hepatolithiasis associated with cholangiocarcinoma [Internet]. World J Surg. 1995;19:637–641.PubMedCrossRef
13.
go back to reference Zhu AX, Lauwers GY, Tanabe KK. Cholangiocarcinoma in association with Thorotrast exposure. J Hepatobiliary Pancreat Surg. 2004;11:430–433.PubMedCrossRef Zhu AX, Lauwers GY, Tanabe KK. Cholangiocarcinoma in association with Thorotrast exposure. J Hepatobiliary Pancreat Surg. 2004;11:430–433.PubMedCrossRef
14.
go back to reference Grainge MJ, West J, Solaymani-Dodaran M, Aithal GP, Card TR. The antecedents of biliary cancer: a primary care case-control study in the United Kingdom. Br J Cancer. 2009;100:178–180.PubMedCentralPubMedCrossRef Grainge MJ, West J, Solaymani-Dodaran M, Aithal GP, Card TR. The antecedents of biliary cancer: a primary care case-control study in the United Kingdom. Br J Cancer. 2009;100:178–180.PubMedCentralPubMedCrossRef
15.
go back to reference Jing W, Jin G, Zhou X, et al. Diabetes mellitus and increased risk of cholangiocarcinoma: a meta-analysis. Eur J Cancer Prev. 2012;21:24–31.PubMedCrossRef Jing W, Jin G, Zhou X, et al. Diabetes mellitus and increased risk of cholangiocarcinoma: a meta-analysis. Eur J Cancer Prev. 2012;21:24–31.PubMedCrossRef
16.
go back to reference Han C, Wu T. Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. J Biol Chem. 2005;280:24053–24063.PubMedCrossRef Han C, Wu T. Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. J Biol Chem. 2005;280:24053–24063.PubMedCrossRef
17.
go back to reference Boonmasawai S, Akarasereenont P, Techatraisak K, Thaworn A, Chotewuttakorn S, Palo T. Effects of selective COX-inhibitors and classical NSAIDs on endothelial cell proliferation and migration induced by human cholangiocarcinoma cell culture [Internet]. J Med Assoc Thai. 2009;92:1508–1515.PubMed Boonmasawai S, Akarasereenont P, Techatraisak K, Thaworn A, Chotewuttakorn S, Palo T. Effects of selective COX-inhibitors and classical NSAIDs on endothelial cell proliferation and migration induced by human cholangiocarcinoma cell culture [Internet]. J Med Assoc Thai. 2009;92:1508–1515.PubMed
18.
go back to reference Liu E, Sakoda LC, Gao YT, et al. Aspirin use and risk of biliary tract cancer: a population-based study in Shanghai, China. Cancer Epidemiol Biomark Prev. 2005;14:1315–1318.CrossRef Liu E, Sakoda LC, Gao YT, et al. Aspirin use and risk of biliary tract cancer: a population-based study in Shanghai, China. Cancer Epidemiol Biomark Prev. 2005;14:1315–1318.CrossRef
19.
go back to reference Shimoyama S. Statins are logical candidates for overcoming limitations of targeting therapies on malignancy: their potential application to gastrointestinal cancers. Cancer Chemother Pharmacol. 2011;67:729–739.PubMedCrossRef Shimoyama S. Statins are logical candidates for overcoming limitations of targeting therapies on malignancy: their potential application to gastrointestinal cancers. Cancer Chemother Pharmacol. 2011;67:729–739.PubMedCrossRef
20.
go back to reference Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from G1 to multiple cell cycles by Lovastatin [Internet]. Cancer Res. 1991;51:3602–3609.PubMed Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from G1 to multiple cell cycles by Lovastatin [Internet]. Cancer Res. 1991;51:3602–3609.PubMed
21.
go back to reference Jakobisiak M, Bruno S, Skierski JS, Darzynkiewicz Z. Cell cycle-specific effects of lovastatin. Proc Natl Acad Sci USA. 1991;1:3628–3632.CrossRef Jakobisiak M, Bruno S, Skierski JS, Darzynkiewicz Z. Cell cycle-specific effects of lovastatin. Proc Natl Acad Sci USA. 1991;1:3628–3632.CrossRef
22.
go back to reference Kamigaki M, Sasaki T, Serikawa M, et al. Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells. Int J Oncol. 2011;39:561–568.PubMed Kamigaki M, Sasaki T, Serikawa M, et al. Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells. Int J Oncol. 2011;39:561–568.PubMed
23.
go back to reference World Health Organization. International statistical classification of diseases and related health problems. 10th revision. M8160/3.C. Geneva: World Health Oganization; 2007. World Health Organization. International statistical classification of diseases and related health problems. 10th revision. M8160/3.C. Geneva: World Health Oganization; 2007.
24.
go back to reference American Joint Committee on Cancer (AJCC). AJCC cancer staging manual. 6th ed. New York, NY: Springer; 2006. American Joint Committee on Cancer (AJCC). AJCC cancer staging manual. 6th ed. New York, NY: Springer; 2006.
25.
go back to reference Muller-Decker K, Furstenberger G. The cyclooxygenase-2-mediated prostaglandin signaling is causally related to epithelial carcinogenesis. Mol Carcinog. 2007;46:705–710.PubMedCrossRef Muller-Decker K, Furstenberger G. The cyclooxygenase-2-mediated prostaglandin signaling is causally related to epithelial carcinogenesis. Mol Carcinog. 2007;46:705–710.PubMedCrossRef
26.
go back to reference Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol. 2001;2:544–551.PubMedCrossRef Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol. 2001;2:544–551.PubMedCrossRef
27.
go back to reference Bhutta HY, Clark A, Holt S, et al. Oesophageal cancer—an aetiological investigation into the potential protective effect of statins in the UK General Practice Research Database (GPRD). Gastroenterology 2011;60:A36-A37. Bhutta HY, Clark A, Holt S, et al. Oesophageal cancer—an aetiological investigation into the potential protective effect of statins in the UK General Practice Research Database (GPRD). Gastroenterology 2011;60:A36-A37.
Metadata
Title
Aspirin May Prevent Cholangiocarcinoma: A Case–Control Study from the United Kingdom
Authors
N. E. Burr
R. J. Talboys
S. Savva
A. Clark
M. Phillips
M. Metcalfe
A. Dennison
R. Robinson
M. P. Lewis
M. Rhodes
S. Rushbrook
A. R. Hart
Publication date
01-07-2014
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2014
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-014-3056-z

Other articles of this Issue 7/2014

Digestive Diseases and Sciences 7/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine