Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study


      Hydrochlorothiazide use has been associated with markedly increased risk for squamous cell carcinoma. No previous studies have investigated the association between hydrochlorothiazide use and the risk for Merkel cell carcinoma (MCC) and malignant adnexal skin tumors (MAST).


      To examine the association between hydrochlorothiazide use and the risk for MCC and MAST.


      Using Danish nationwide health registries, we identified all patients with incident MCC or MAST during 2004-2015 and matched the cases individually to cancer-free population controls by risk set sampling. Using conditional logistic regression, we estimated the odds ratios (ORs) and confidence intervals (CIs) associated with cumulative use of hydrochlorothiazide.


      The adjusted ORs for MCC and MAST associated with high use (≥50,000 mg) of hydrochlorothiazide was 2.3 (95% CI 1.1-4.8) and 3.6 (95% CI 1.9-7.0), respectively, which increased to 3.3 (95% CI 1.3-8.3) and 5.6 (95% CI 2.4-13.3), respectively, with highest use (≥100,000 mg). We found no increased risk for these tumors in analyses of drugs with similar indications as hydrochlorothiazide, except there was a tendency toward an increased risk for MCC associated with the use of furosemide (OR 1.9, 95% CI 0.9-4.0).


      No data on sun exposure was available.


      Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.

      Key words

      Abbreviations used:

      CI (confidence interval), OR (odds ratio), UV (ultraviolet)
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        • Wang Y.R.
        Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States.
        Arch Intern Med. 2007; 167: 141-147
        • Gu Q.
        • Burt V.L.
        • Dillon C.F.
        • Yoon S.
        Trends in Antihypertensive medication use and blood pressure control among United States adults with hypertension clinical perspective.
        Circulation. 2012; 126: 2105-2114
        • Moore D.
        e. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management.
        Drug Saf. 2002; 25: 345-372
        • Pottegård A.
        • Pedersen S.A.
        • Schmidt S.A.J.
        • Hölmich L.R.
        • Friis S.
        • Gaist D.
        Association of hydrochlorothiazide use and risk of malignant melanoma.
        JAMA Intern Med. 2018; 178: 1120-1122
        • Pottegård A.
        • Hallas J.
        • Olesen M.
        • et al.
        Hydrochlorothiazide use is strongly associated with risk of lip cancer.
        J Intern Med. 2017;
        • Pedersen S.A.
        • Gaist D.
        • Schmidt S.A.J.
        • Hölmich L.R.
        • Friis S.
        • Pottegård A.
        Hydrochlorothiazide use and risk of nonmelanoma skin cancer: a nationwide case-control study from Denmark.
        J Am Acad Dermatol. 2017;
        • Miller R.W.
        • Rabkin C.S.
        Merkel Cell carcinoma and melanoma: etiological similarities and differences.
        Cancer Epidemiol Biomarkers Prev. 1999; 8 (Available at:)
        • Robertson J.P.
        • Liang E.S.
        • Martin R.C.W.
        Epidemiology of Merkel cell carcinoma in New Zealand: a population-based study.
        Br J Dermatol. 2015; 173: 835-837
        • Martinez S.R.
        • Barr K.L.
        • Canter R.J.
        Rare tumors through the looking glass: an examination of malignant cutaneous adnexal tumors.
        Arch Dermatol. 2011; 147: 1058-1062
        • Feng H.
        • Shuda M.
        • Chang Y.
        • Moore P.S.
        Clonal integration of a polyomavirus in human Merkel cell carcinoma.
        Science. 2008; 319: 1096-1100
        • Blake P.W.
        • Bradford P.T.
        • Devesa S.S.
        • Toro J.R.
        Cutaneous appendageal carcinoma incidence and survival patterns in the United States: a population-based study.
        Arch Dermatol. 2010; 146: 625-632
        • Stam H.
        • Lohuis P.J.F.M.
        • Zupan-Kajcovski B.
        • Wouters M.W.J.M.
        • van der Hage JA.
        • Visser O.
        Increasing incidence and survival of a rare skin cancer in the Netherlands. A population-based study of 2,220 cases of skin adnexal carcinoma.
        J Surg Oncol. 2013; 107: 822-827
        • Gopinath S.
        • Giambarberi L.
        • Patil S.
        • Chamberlain R.S.
        Characteristics and survival of patients with eccrine carcinoma: a cohort study.
        J Am Acad Dermatol. 2016; 75: 215-217
        • Mallone S.
        • De Vries E.
        • Guzzo M.
        • Virgili G.
        Descriptive epidemiology of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe.
        Eur J Cancer. 2012; 48
        • Kaae J.
        • Boyd H.A.
        • Hansen A.V.
        • Wulf H.C.
        • Wohlfahrt J.
        • Melbye M.
        Photosensitizing medication use and risk of skin cancer.
        Cancer Epidemiol Biomarkers Prev. 2010; 19: 2942-2949
        • Gjerstorff M.L.
        The Danish Cancer Registry.
        Scand J Public Health. 2011; 39: 42-45
        • Schmidt S.A.J.
        • Schmidt M.
        • Mehnert F.
        • Lemeshow S.
        • Sørensen H.T.
        Use of antihypertensive drugs and risk of skin cancer.
        J Eur Acad Dermatol Venereol. 2015; 29: 1545-1554
        • Robinson S.N.
        • Zens M.S.
        • Perry A.E.
        • Spencer S.K.
        • Duell E.J.
        • Karagas M.R.
        Photosensitizing agents and the risk of non-melanoma skin cancer: a population-based case–control study.
        J Invest Dermatol. 2013; 133: 1950-1955
        • AØ Jensen
        • Thomsen H.F.
        • Engebjerg M.C.
        • Olesen A.B.
        • Sørensen H.T.
        • Karagas M.R.
        Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study.
        Br J Cancer. 2008; 99: 1522-1528
        • Egeberg A.
        • Thyssen J.p.
        • Gislason G.h.
        • Skov L.
        Skin cancer in patients with psoriasis.
        J Eur Acad Dermatol Venereol. 2016;
        • Tennis P.
        • Gelfand J.M.
        • Rothman K.J.
        Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors: cancer, eczema and topical calcineurin inhibitors.
        Br J Dermatol. 2011; 165: 465-473
      1. International Agency for Research on Cancer; World Health Organization. Some drugs and herbal products. Volume 108. IARC monographs on the evaluation of carcinogenic risks to humans. Available at: Accessed December 7, 2018.

        • Lemos B.D.
        • Storer B.E.
        • Iyer J.G.
        • et al.
        Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system.
        J Am Acad Dermatol. 2010; 63: 751-761

      Linked Article

      • Thiazides and nonmelanoma skin cancer: Is it a class effect?
        Journal of the American Academy of DermatologyVol. 82Issue 1
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          To the Editor: We read with interest the article by Pedersen et al,1 who studied the association between hydrochlorothiazide (HTZ) use and the risk of nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). To further assess this association and to study NMSC as a possible thiazide class effect, we searched in VigiBase, the World Health Organization's pharmacovigilance database, for thiazide-associated reports associated with the preferred terms BCC and SCC from the Medical Dictionary for Regulatory Activities from January 1, 2004, to December 31, 2012.
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