Skip to main content
Top
Published in: Drug Safety 3/2017

01-03-2017 | Original Research Article

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study

Authors: Beatrice Nardone, Sara Majewski, Ashley S. Kim, Tina Kiguradze, Estela M. Martinez-Escala, Rivka Friedland, Ahmad Amin, Anne E. Laumann, Beatrice J. Edwards, Alfred W. Rademaker, Mary C. Martini, Dennis P. West

Published in: Drug Safety | Issue 3/2017

Login to get access

Abstract

Introduction

Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

Objective

The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers.

Methods

This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses.

Results

Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35).

Conclusions

A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.
Appendix
Available only for authorised users
Literature
1.
3.
go back to reference Jensen AO, Thomsen HF, Engebjerg MC, Olesen AB, Sorensen HT, Karagas MR. Use of photosensitising diuretics and risk of skin cancer: a population-based case-control study. Br J Cancer. 2008;99(9):1522–8.CrossRefPubMedPubMedCentral Jensen AO, Thomsen HF, Engebjerg MC, Olesen AB, Sorensen HT, Karagas MR. Use of photosensitising diuretics and risk of skin cancer: a population-based case-control study. Br J Cancer. 2008;99(9):1522–8.CrossRefPubMedPubMedCentral
4.
go back to reference Koomen ER, Herings RM, Guchelaar HJ, Nijsten T. Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cancer Epidemiol. 2009;33(5):391–5.CrossRefPubMed Koomen ER, Herings RM, Guchelaar HJ, Nijsten T. Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cancer Epidemiol. 2009;33(5):391–5.CrossRefPubMed
5.
go back to reference Schmidt SA, Schmidt M, Mehnert F, Lemeshow S, Sorensen HT. Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol. 2015;29(8):1545–54.CrossRefPubMed Schmidt SA, Schmidt M, Mehnert F, Lemeshow S, Sorensen HT. Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol. 2015;29(8):1545–54.CrossRefPubMed
6.
go back to reference Yoon C, Yang HS, Jeon I, Chang Y, Park SM. Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies. CMAJ. 2011;183(14):E1073–84.CrossRefPubMedPubMedCentral Yoon C, Yang HS, Jeon I, Chang Y, Park SM. Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies. CMAJ. 2011;183(14):E1073–84.CrossRefPubMedPubMedCentral
7.
go back to reference Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010;11(7):627–36.CrossRefPubMedPubMedCentral Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010;11(7):627–36.CrossRefPubMedPubMedCentral
9.
go back to reference Lindberg H, Nielsen D, Jensen BV, Eriksen J, Skovsgaard T. Angiotensin converting enzyme inhibitors for cancer treatment? Acta Oncol. 2004;43(2):142–52.CrossRefPubMed Lindberg H, Nielsen D, Jensen BV, Eriksen J, Skovsgaard T. Angiotensin converting enzyme inhibitors for cancer treatment? Acta Oncol. 2004;43(2):142–52.CrossRefPubMed
10.
go back to reference McKoy JM, Fisher MJ, Courtney DM, Raisch DW, Edwards BJ, Scheetz MH, et al. Results from the first decade of research conducted by the Research on Adverse Drug Events and Reports (RADAR) project. Drug Saf. 2013;36(5):335–47.CrossRefPubMedPubMedCentral McKoy JM, Fisher MJ, Courtney DM, Raisch DW, Edwards BJ, Scheetz MH, et al. Results from the first decade of research conducted by the Research on Adverse Drug Events and Reports (RADAR) project. Drug Saf. 2013;36(5):335–47.CrossRefPubMedPubMedCentral
11.
go back to reference Starren JB, Winter AQ, Lloyd-Jones DM. Enabling a learning health system through a unified enterprise data warehouse: the Experience of the Northwestern University Clinical and Translational Sciences (NUCATS) Institute. Clin Transl Sci. 2015;8(4):269–71.CrossRefPubMedPubMedCentral Starren JB, Winter AQ, Lloyd-Jones DM. Enabling a learning health system through a unified enterprise data warehouse: the Experience of the Northwestern University Clinical and Translational Sciences (NUCATS) Institute. Clin Transl Sci. 2015;8(4):269–71.CrossRefPubMedPubMedCentral
12.
go back to reference Naldi L, Fortina AB, Lovati S, Barba A, Gotti E, Tessari G, et al. Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study. Transplantation. 2000;70(10):1479–84.CrossRefPubMed Naldi L, Fortina AB, Lovati S, Barba A, Gotti E, Tessari G, et al. Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study. Transplantation. 2000;70(10):1479–84.CrossRefPubMed
13.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40(5):373–83.CrossRefPubMed Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40(5):373–83.CrossRefPubMed
14.
go back to reference Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45(6):613–9.CrossRefPubMed Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45(6):613–9.CrossRefPubMed
15.
go back to reference Agresti A. Categorical data analysis, 3rd ed. Hoboken: Wiley; 2013. Agresti A. Categorical data analysis, 3rd ed. Hoboken: Wiley; 2013.
18.
go back to reference SAS Institute Inc. SAS OnlineDoc® 9.4. Cary: SAS Institute Inc; 2012. SAS Institute Inc. SAS OnlineDoc® 9.4. Cary: SAS Institute Inc; 2012.
19.
go back to reference Moscarelli L, Zanazzi M, Mancini G, Rossi E, Caroti L, Rosso G, et al. Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients. Clin Nephrol. 2010;73(6):439–45.CrossRefPubMed Moscarelli L, Zanazzi M, Mancini G, Rossi E, Caroti L, Rosso G, et al. Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients. Clin Nephrol. 2010;73(6):439–45.CrossRefPubMed
20.
go back to reference Christian JB, Lapane KL, Hume AL, Eaton CB, Weinstock MA, Trial V. Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte cancer prevention in the randomized VATTC trial. J Natl Cancer Inst. 2008;100(17):1223–32.CrossRefPubMed Christian JB, Lapane KL, Hume AL, Eaton CB, Weinstock MA, Trial V. Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte cancer prevention in the randomized VATTC trial. J Natl Cancer Inst. 2008;100(17):1223–32.CrossRefPubMed
21.
go back to reference McDonald E, Freedman DM, Alexander BH, Doody MM, Tucker MA, Linet MS, et al. Prescription diuretic use and risk of basal cell carcinoma in the nationwide U.S. radiologic technologists cohort. Cancer Epidemiol Biomark Prev. 2014;23(8):1539–45.CrossRef McDonald E, Freedman DM, Alexander BH, Doody MM, Tucker MA, Linet MS, et al. Prescription diuretic use and risk of basal cell carcinoma in the nationwide U.S. radiologic technologists cohort. Cancer Epidemiol Biomark Prev. 2014;23(8):1539–45.CrossRef
23.
go back to reference Walther T, Menrad A, Orzechowski HD, Siemeister G, Paul M, Schirner M. Differential regulation of in vivo angiogenesis by angiotensin II receptors. FASEB J. 2003;17(14):2061–7.CrossRefPubMed Walther T, Menrad A, Orzechowski HD, Siemeister G, Paul M, Schirner M. Differential regulation of in vivo angiogenesis by angiotensin II receptors. FASEB J. 2003;17(14):2061–7.CrossRefPubMed
Metadata
Title
Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study
Authors
Beatrice Nardone
Sara Majewski
Ashley S. Kim
Tina Kiguradze
Estela M. Martinez-Escala
Rivka Friedland
Ahmad Amin
Anne E. Laumann
Beatrice J. Edwards
Alfred W. Rademaker
Mary C. Martini
Dennis P. West
Publication date
01-03-2017
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 3/2017
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-016-0487-9

Other articles of this Issue 3/2017

Drug Safety 3/2017 Go to the issue