Chronic Use of Hydrochlorothiazide and Risk of Skin Cancer in Caucasian Adults: A PharmLines Initiative Inception Cohort Study

Authors

  • Marjolijn S. Haisma Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Nathalie Greven Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Mathanhy Logendran Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Jens Bos Groningen Research Institute of Pharmacy, Unit PharmacoTherapy, -Epidemiology &-Economics, University of Groningen, Groningen, The Netherlands
  • Bert van der Vegt Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Barbara Horváth Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Stijn de Vos Groningen Research Institute of Pharmacy, Unit PharmacoTherapy, -Epidemiology &-Economics, University of Groningen, Groningen, The Netherlands
  • Geertruida H. de Bock Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Eelko Hak Groningen Research Institute of Pharmacy, Unit PharmacoTherapy, -Epidemiology &-Economics, University of Groningen, Groningen, The Netherlands
  • Emőke Rácz Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

DOI:

https://doi.org/10.2340/actadv.v103.3933

Keywords:

basal cell carcinoma, hydrochlorothiazide, skin cancer, squamous cell carcinoma

Abstract

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n =608), subjects starting treatment with other antihypertensives (n =508), and non-antihypertensive long-term medication users (n =1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40–11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12–17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11–19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12–123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults. 

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References

Akbari P, Khorasani-Zadeh A. Thiazide diuretics. 2021 Jul 13. In: StatPearls. Treasure Island (FL): 2022 Jan. [Assessed on 30 June 2022] Available at: https://www.statpearls.com/point-of-care/30055.

Wang YR, Alexander, G Caleb, Stafford RS. Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Available at https://jamanetwork.com/

George EA, Baranwal N, Kang JH, Qureshi AA, Drucker AM, Cho E. Photosensitizing medications and skin cancer: a comprehensive review. Cancers (Basel). MDPI; 2021.

https://doi.org/10.3390/cancers13102344 DOI: https://doi.org/10.3390/cancers13102344

Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B. 2001; 63: 8-18.

https://doi.org/10.1016/S1011-1344(01)00198-1 DOI: https://doi.org/10.1016/S1011-1344(01)00198-1

Shin D, Lee ES, Kim J, Guerra L, Naik D, Prida X. Association between the use of thiazide diuretics and the risk of skin cancers: a meta-analysis of observational studies. J Clin Med Res 2019; 11: 247-255.

https://doi.org/10.14740/jocmr3744 DOI: https://doi.org/10.14740/jocmr3744

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: 1545-1554.

https://doi.org/10.1111/jdv.12921

Ruiter R, Visser LE, Eijgelsheim M, Rodenburg EM, Hofman A, Coebergh JWW, 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: 2467-2472.

https://doi.org/10.1016/j.ejca.2010.04.024 DOI: https://doi.org/10.1016/j.ejca.2010.04.024

Sediq R, van der Schans J, Dotinga A, Alingh RA, Wilffert B, Bos JHJ, et al. Concordance assessment of self-reported medication use in the netherlands three-generation lifelines cohort study with the pharmacy database iadb.Nl: the pharmlines initiative. Clin Epidemiol Dove 2018; 10: 981-989.

https://doi.org/10.2147/CLEP.S163037 DOI: https://doi.org/10.2147/CLEP.S163037

IADB. Background. Visited on 15 November 2021. Available via: https: //www.iadb.nl/

Scholtens S, Smidt N, Swertz MA, Bakker SJL, Dotinga A, Vonk JM, et al. Cohort Profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol 2015; 44: 1172-1180.

https://doi.org/10.1093/ije/dyu229 DOI: https://doi.org/10.1093/ije/dyu229

Casparie M, Tiebosch ATMG, Burger G, Blauwgeers H, van de Pol A, van Krieken JHJM, et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol 2007; 29: 19-24.

https://doi.org/10.1155/2007/971816 DOI: https://doi.org/10.1155/2007/971816

Centraal Bureau voor de Statistiek (CBS). CBS home. [Assessed on 06 June 2021] Available at: https://www.cbs.nl/nl-nl

Gloster HM, Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol 2006; 55: 741-764.

https://doi.org/10.1016/j.jaad.2005.08.063 DOI: https://doi.org/10.1016/j.jaad.2005.08.063

Adami J, Gäbel H, Lindelöf B, Ekström K, Rydh B, Glimelius B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 2003; 89: 1221-1227.

https://doi.org/10.1038/sj.bjc.6601219 DOI: https://doi.org/10.1038/sj.bjc.6601219

Wilkins K, Turner R, Dolev JC, LeBoit PE, Berger TG, Maurer TA. Cutaneous malignancy and human immunodeficiency virus disease. J Am Acad Dermatol 2006; 54: 189-206.

https://doi.org/10.1016/j.jaad.2004.11.060 DOI: https://doi.org/10.1016/j.jaad.2004.11.060

Royle JA, Baade PD, Joske D, Girschik J, Fritschi L. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer 2011; 105: 1076-1081.

https://doi.org/10.1038/bjc.2011.313 DOI: https://doi.org/10.1038/bjc.2011.313

Pottegård A, Hallas J. New use of prescription drugs prior to a cancer diagnosis. Pharmacoepidemiol Drug Saf 2017; 26: 223-227.

https://doi.org/10.1002/pds.4145 DOI: https://doi.org/10.1002/pds.4145

Jensen A, 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: 1522-1528.

https://doi.org/10.1038/sj.bjc.6604686 DOI: https://doi.org/10.1038/sj.bjc.6604686

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: 673-681.

https://doi.org/10.1016/j.jaad.2017.11.042 DOI: https://doi.org/10.1016/j.jaad.2017.11.042

Pottegård A, Hallas J, Olesen M, Svendsen MT, Habel LA, Friedman GD, et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer 2017; 282: 322-331.

https://doi.org/10.1111/joim.12629 DOI: https://doi.org/10.1111/joim.12629

Rouette J, Yin H, Pottegård A, Nirantharakumar K, Azoulay L. Use of hydrochlorothiazide and risk of melanoma and nonmelanoma skin cancer. Drug Saf 2021; 44: 245-254.

https://doi.org/10.1007/s40264-020-01015-1

Schneider R, Reinau D, Stoffel S, Jick SS, Meier CR, Spoendlin J. Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group*. Br J Dermatol 2021; 185: 343-352.

https://doi.org/10.1111/bjd.19880 DOI: https://doi.org/10.1111/bjd.19880

Su KA, Habel LA, Achacoso NS, Friedman GD, Asgari MM. Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma. Br J Dermatol 2018; 179: 1088-1094.

https://doi.org/10.1111/bjd.16713 DOI: https://doi.org/10.1111/bjd.16713

Pottegård A, Pedersen SA, Schmidt SAJ, Lee CN, Hsu CK, Liao TC, et al. Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study. Br J Cancer 2019; 121: 973-978.

https://doi.org/10.1038/s41416-019-0613-4 DOI: https://doi.org/10.1038/s41416-019-0613-4

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 2020; 35: 917-928.

https://doi.org/10.3904/kjim.2019.218 DOI: https://doi.org/10.3904/kjim.2019.218

Rosso S, Zanetti R, Martinez C, Tormo MJ, Schraub S, Sancho-Garnier H, et al. The multicentre south European study "Helios". II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin. Br J Cancer 1996; 73: 1447-1454.

https://doi.org/10.1038/bjc.1996.275 DOI: https://doi.org/10.1038/bjc.1996.275

Rouette J, Yin H, Pottegård A, Nirantharakumar K, Azoulay L. Use of hydrochlorothiazide and risk of melanoma and nonmelanoma skin cancer. Drug Saf 2021; 44: 245-254.

https://doi.org/10.1007/s40264-020-01015-1 DOI: https://doi.org/10.1007/s40264-020-01015-1

Medicines Evaluation Board. Hydrochloorthiazide. [Assessed on 15 Nov 2021] Available from: https://www.cbg-meb.nl/documenten/videos/2018/10/30/hct-ton-de-boer.

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: 1545-1554.

https://doi.org/10.1111/jdv.12921 DOI: https://doi.org/10.1111/jdv.12921

Additional Files

Published

2023-04-04

How to Cite

Haisma, M. S., Greven, N. ., Logendran, M., Bos, J., van der Vegt, B., Horváth, B., de Vos, S., de Bock, G. H., Hak, E., & Rácz, E. (2023). Chronic Use of Hydrochlorothiazide and Risk of Skin Cancer in Caucasian Adults: A PharmLines Initiative Inception Cohort Study. Acta Dermato-Venereologica, 103, adv3933. https://doi.org/10.2340/actadv.v103.3933

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