Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

Author(s): Luca Gallelli, Erika Cione, Antonio Siniscalchi*, Gianfranco Vasta, Antonio Guerra, Andrea Scaramuzzino, Lucia Longo, Lucia Muraca, Giovambattista De Sarro, “G & SP” Working Group, Giacomo Leuzzi, Antonio Gerace, Antonio Scuteri, Piero Vasapollo, Vincenzo Natale, Stefania Zampogna and Filippo Luciani

Volume 17, Issue 3, 2022

Published on: 17 March, 2022

Page: [211 - 216] Pages: 6

DOI: 10.2174/1574886316666211103164412

Price: $65

Abstract

Aims: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

Background: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability.

Objective: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC.

Methods: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression.

Results: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC.

Conclusion: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Keywords: Hydrochlorothiazide, non-melanoma, skin cancer, hypertension, pharmacology, BCC, SCC.

Graphical Abstract

[1]
Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39(33): 3021-104.
[http://dx.doi.org/10.1093/eurheartj/ehy339] [PMID: 30165516]
[2]
Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension global hypertension practice guidelines. Hypertension 2020; 75(6): 1334-57.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15026] [PMID: 32370572]
[3]
Roush GC, Messerli FH. Chlorthalidone versus hydrochlorothiazide: Major cardiovascular events, blood pressure, left ventricular mass, and adverse effects. J Hypertens 2021; 39(6): 1254-60.
[http://dx.doi.org/10.1097/HJH.0000000000002771] [PMID: 33470735]
[4]
Pottegård A, Hallas J, Olesen M, et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 2017; 282(4): 322-31.
[http://dx.doi.org/10.1111/joim.12629] [PMID: 28480532]
[5]
Pedersen SA, Johannesdottir Schmidt SA, Hölmich LR, Friis S, Pottegård A, Gaist D. Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study. J Am Acad Dermatol 2019; 80(2): 460-465.e9.
[http://dx.doi.org/10.1016/j.jaad.2018.06.014] [PMID: 29913261]
[6]
Jahan-Tigh RR, Huen AO, Lee GL, Pozadzides JV, Liu P, Duvic M. Hydrochlorothiazide and cutaneous T cell lymphoma: Prospective analysis and case series. Cancer 2013; 119(4): 825-31.
[http://dx.doi.org/10.1002/cncr.27740] [PMID: 22952039]
[7]
Bendinelli B, Masala G, Garamella G, Palli D, Caini S. Do thiazide diuretics increase the risk of skin cancer? a critical review of the scientific evidence and updated meta-analysis. Curr Cardiol Rep 2019; 21(9): 92.
[http://dx.doi.org/10.1007/s11886-019-1183-z] [PMID: 31352643]
[8]
Schmidt SAJ, Schmidt M, Mehnert F, Lemeshow S, Sørensen HT. Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol 2015; 29(8): 1545-54.
[http://dx.doi.org/10.1111/jdv.12921] [PMID: 25640031]
[9]
Cassano N, Di Stefani A, Vena GA, Peris K. Antihypertensive drugs and risk of skin cancer. G Ital Dermatol Venereol 2018; 153(5): 672-84.
[http://dx.doi.org/10.23736/S0392-0488.18.05870-4] [PMID: 29368863]
[10]
Ruiter R, Visser LE, Eijgelsheim M, et al. High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study. Eur J Cancer 2010; 46(13): 2467-72.
[http://dx.doi.org/10.1016/j.ejca.2010.04.024] [PMID: 20605443]
[11]
Jensen AØ, Thomsen HF, Engebjerg MC, Olesen AB, Sørensen 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.
[http://dx.doi.org/10.1038/sj.bjc.6604686] [PMID: 18813314]
[12]
Robinson SN, Zens MS, Perry AE, Spencer SK, Duell EJ, Karagas MR. Photosensitizing agents and the risk of non-melanoma skin cancer: A population-based case-control study. J Invest Dermatol 2013; 133(8): 1950-5.
[http://dx.doi.org/10.1038/jid.2013.33] [PMID: 23344461]
[13]
Pedersen SA, Gaist D, Schmidt SAJ, Hölmich LR, Friis S, Pottegård A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018; 78(4): 673-681.e9.
[http://dx.doi.org/10.1016/j.jaad.2017.11.042] [PMID: 29217346]
[14]
IARC working Group on the evaluation of carcinogenic Risks to Humans Some Drugs and Herbal Products. 2016. IARC Monogr Eval Carcinog Risks Hum. 2004;84:1-477.
[15]
Medicines Agency E. Minutes of PRAC meeting on 03-06 September 2018 2018.
[16]
Gandini S, Palli D, Spadola G, et al. Anti-hypertensive drugs and skin cancer risk: A review of the literature and meta-analysis. Crit Rev Oncol Hematol 2018; 122: 1-9.
[http://dx.doi.org/10.1016/j.critrevonc.2017.12.003] [PMID: 29458778]
[17]
Kaae J, Boyd HA, Hansen AV, Wulf HC, Wohlfahrt J, Melbye M. Photosensitizing medication use and risk of skin cancer. Cancer Epidemiol Biomarkers Prev 2010; 19(11): 2942-9.
[http://dx.doi.org/10.1158/1055-9965.EPI-10-0652] [PMID: 20861398]
[18]
Staltari O, Cilurzo F, Caroleo B, et al. Annual report on adverse events related with vaccines use in Calabria (Italy): 2012. J Pharmacol Pharmacother 2013; 4(Suppl. 1): S61-5.
[http://dx.doi.org/10.4103/0976-500X.120951] [PMID: 24347985]
[19]
Rende P, Paletta L, Gallelli G, et al. Retrospective evaluation of adverse drug reactions induced by antihypertensive treatment. J Pharmacol Pharmacother 2013; 4(Suppl. 1): S47-50.
[http://dx.doi.org/10.4103/0976-500X.120954] [PMID: 24347982]
[20]
Zanon D, Gallelli L, Rovere F, et al. Off-label prescribing patterns of antiemetics in children: A multicenter study in Italy. Eur J Pediatr 2013; 172(3): 361-7.
[http://dx.doi.org/10.1007/s00431-012-1894-2] [PMID: 23207736]
[21]
Gallelli L, Ferreri G, Colosimo M, et al. Retrospective analysis of adverse drug reactions to bronchodilators observed in two pulmonary divisions of Catanzaro, Italy. Pharmacol Res 2003; 47(6): 493-9.
[http://dx.doi.org/10.1016/S1043-6618(03)00003-3] [PMID: 12742002]
[22]
Gallelli L, Colosimo M, Pirritano D, et al. Retrospective evaluation of adverse drug reactions induced by nonsteroidal anti-inflammatory drugs. Clin Drug Investig 2007; 27(2): 115-22.
[http://dx.doi.org/10.2165/00044011-200727020-00004] [PMID: 17217316]
[23]
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30(2): 239-45.
[http://dx.doi.org/10.1038/clpt.1981.154] [PMID: 7249508]
[24]
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother 2007; 41(4): 674-80.
[http://dx.doi.org/10.1345/aph.1H423] [PMID: 17389673]
[25]
Gallelli L, Avenoso T, Falcone D, et al. Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium. Headache 2014; 54(2): 313-24.
[http://dx.doi.org/10.1111/head.12162] [PMID: 23808884]
[26]
Gallelli L, De Fazio S, Corace E, De Sarro G, Garcia CS, De Fazio P. Generalised urticaria in a young woman treated with clomipramine and after ingestion of codfish. Pharmacopsychiatry 2006; 39(4): 154-6.
[http://dx.doi.org/10.1055/s-2006-946707] [PMID: 16871472]
[27]
Russo R, Gallelli L, Cannataro R, et al. When nutraceuticals reinforce drugs side effects: a case report. Curr Drug Saf 2016; 11(3): 264-6.
[http://dx.doi.org/10.2174/1574886311666160201152047] [PMID: 26830519]
[28]
Caroleo B, Staltari O, Gallelli L, Perticone F. Reactivation of chronic hepatitis B during treatment with tenofovir disoproxil fumarate: Drug interactions or low adherence? BMJ Case Rep 2015 2015.
[http://dx.doi.org/10.1136/bcr-2015-209586]
[29]
Serra R, Grande R, Butrico L, et al. Effects of a new nutraceutical substance on clinical and molecular parameters in patients with chronic venous ulceration. Int Wound J 2016; 13(1): 88-96.
[http://dx.doi.org/10.1111/iwj.12240] [PMID: 24612734]
[30]
Gallelli L, Staltari O, Palleria C, De Sarro G, Ferraro M. Hepatotoxicity induced by methimazole in a previously healthy patient. Curr Drug Saf 2009; 4(3): 204-6.
[http://dx.doi.org/10.2174/157488609789006912] [PMID: 19534646]
[31]
Thestrup-Pedersen K. Adverse reactions in the skin from anti-hypertensive drugs. Dan Med Bull 1987; 34(Suppl. 1): 3-5.
[PMID: 2893692]
[32]
Han KD, Bark K-M, Heo EP, Lee JK, Kang JS, Kim TH. Increased phototoxicity of hydrochlorothiazide by photodegradation. Photodermatol Photoimmunol Photomed 2000; 16(3): 121-4.
[http://dx.doi.org/10.1034/j.1600-0781.2000.d01-17.x] [PMID: 10885441]
[33]
Kunisada M, Masaki T, Ono R, et al. Hydrochlorothiazide enhances UVA-induced DNA damage. Photochem Photobiol 2013; 89(3): 649-54.
[http://dx.doi.org/10.1111/php.12048] [PMID: 23331297]
[34]
Kreutz R, Algharably EAH, Douros A. Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer. J Hypertens 2019; 37(10): 1950-8.
[http://dx.doi.org/10.1097/HJH.0000000000002136] [PMID: 31145177]
[35]
Garrido PM, Borges-Costa J. Hydrochlorothiazide treatment and risk of non-melanoma skin cancer: Review of the literature. Rev Port Cardiol 2020; 39(3): 163-70.
[http://dx.doi.org/10.1016/j.repce.2019.07.006] [PMID: 32354458]
[36]
Park E, Lee Y, Jue MS. Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: A nationwide retrospective cohort study from Korea. Korean J Intern Med (Korean Assoc Intern Med) 2020; 35(4): 917-28.
[http://dx.doi.org/10.3904/kjim.2019.218] [PMID: 31842528]
[37]
Scicchitano F, Giofrè C, Palleria C, et al. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis. J Res Med Sci 2012; 17(9): 872-5.
[PMID: 23826016]
[38]
Mohebbi N, Shalviri G, Salarifar M, Salamzadeh J, Gholami K. Adverse drug reactions induced by cardiovascular drugs in cardiovascular care unit patients. Pharmacoepidemiol Drug Saf 2010; 19(9): 889-94.
[http://dx.doi.org/10.1002/pds.1916] [PMID: 20146242]
[39]
Treudler R. WFAPSJ. Adverse drug reactions in elderly people : First data from the Leipzig Research Center for Civilization Diseases (LIFE). Hautarzt 2017; 68(1): 5-11.
[40]
Kanagaratnam L, Dramé M, Novella JL, et al. Risk factors for adverse drug reactions in older subjects hospitalized in a dedicated dementia unit. Am J Geriatr Psychiatry 2017; 25(3): 290-6.
[http://dx.doi.org/10.1016/j.jagp.2016.07.002] [PMID: 27742527]
[41]
Gallelli L, Nardi M, Prantera T, et al. Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer. Pharmacol Res 2004; 49(3): 259-63.
[http://dx.doi.org/10.1016/j.phrs.2003.10.001] [PMID: 14726222]
[42]
Carrasco-Garrido P, Hernández-Barrera V, Esteban-Hernández J, et al. Adverse drug reactions to anticoagulants in spain: analysis of the spanish national hospital discharge data (2010-2013). BMJ Open 2017; 7(1): e013224.
[http://dx.doi.org/10.1136/bmjopen-2016-013224] [PMID: 28073793]
[43]
Rodenburg EM, Stricker BH, Visser LE. Sex differences in cardiovascular drug-induced adverse reactions causing hospital admissions. Br J Clin Pharmacol 2012; 74(6): 1045-52.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04310.x] [PMID: 22533339]
[44]
Rodenburg EM, Stricker BHC, Visser LE. Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. Br J Clin Pharmacol 2011; 71(1): 95-104.
[http://dx.doi.org/10.1111/j.1365-2125.2010.03811.x] [PMID: 21143505]
[45]
Gallelli L, Ferreri G, Colosimo M, et al. Adverse drug reactions to antibiotics observed in two pulmonology divisions of catanzaro, Italy: A six-year retrospective study. Pharmacol Res 2002; 46(5): 395-400.
[http://dx.doi.org/10.1016/S1043661802002104] [PMID: 12419643]
[46]
Venturini CD, Engroff P, Ely LS, et al. Gender differences, polypharmacy, and potential pharmacological interactions in the elderly. Clinics (São Paulo) 2011; 66(11): 1867-72.
[PMID: 22086515]
[47]
Chen YC, Fan JS, Chen MH, et al. Risk factors associated with adverse drug events among older adults in emergency department. Eur J Intern Med 2014; 25(1): 49-55.
[http://dx.doi.org/10.1016/j.ejim.2013.10.006] [PMID: 24200546]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy