Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors

A nationwide case-control study

Sidsel Arnspang Pedersen, Sigrun Alba Johannesdottir Schmidt, Lisbet Rosenkrantz Hölmich, Søren Friis, Anton Pottegård, David Gaist

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Abstract

Background: 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). Objective: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. Methods: 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. Results: 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). Limitations: No data on sun exposure was available. Conclusion: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.

Original languageEnglish
JournalJournal of the American Academy of Dermatology
Volume80
Issue number2
Pages (from-to)460-465.e9
ISSN0190-9622
DOIs
Publication statusPublished - Feb 2019

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Merkel Cell Carcinoma
Case-Control Studies
Skin
Confidence Intervals
Neoplasms
Odds Ratio
Population Control
Furosemide
Registries
Logistic Models
Health

Keywords

  • Merkel cell carcinoma
  • antihypertensives
  • epidemiology
  • hydrochlorothiazide
  • malignant adnexal skin tumors
  • pharmacology
  • skin cancer
  • Multivariate Analysis
  • Age Distribution
  • Prognosis
  • Humans
  • Middle Aged
  • Male
  • Skin Neoplasms/chemically induced
  • Case-Control Studies
  • Incidence
  • Dose-Response Relationship, Drug
  • Carcinoma, Merkel Cell/chemically induced
  • Aged, 80 and over
  • Female
  • Hypertension/diagnosis
  • Registries
  • Retrospective Studies
  • Odds Ratio
  • Hydrochlorothiazide/adverse effects
  • Risk Assessment
  • Logistic Models
  • Neoplasms, Adnexal and Skin Appendage/chemically induced
  • Survival Analysis
  • Denmark
  • Sex Distribution
  • Aged

Cite this

@article{c309293bebb241c696be2b651668370d,
title = "Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study",
abstract = "Background: 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). Objective: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. Methods: 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. Results: 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). Limitations: No data on sun exposure was available. Conclusion: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.",
keywords = "Merkel cell carcinoma, antihypertensives, epidemiology, hydrochlorothiazide, malignant adnexal skin tumors, pharmacology, skin cancer, Multivariate Analysis, Age Distribution, Prognosis, Humans, Middle Aged, Male, Skin Neoplasms/chemically induced, Case-Control Studies, Incidence, Dose-Response Relationship, Drug, Carcinoma, Merkel Cell/chemically induced, Aged, 80 and over, Female, Hypertension/diagnosis, Registries, Retrospective Studies, Odds Ratio, Hydrochlorothiazide/adverse effects, Risk Assessment, Logistic Models, Neoplasms, Adnexal and Skin Appendage/chemically induced, Survival Analysis, Denmark, Sex Distribution, Aged",
author = "Pedersen, {Sidsel Arnspang} and {Johannesdottir Schmidt}, {Sigrun Alba} and H{\"o}lmich, {Lisbet Rosenkrantz} and S{\o}ren Friis and Anton Potteg{\aa}rd and David Gaist",
note = "Copyright {\circledC} 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "2",
doi = "10.1016/j.jaad.2018.06.014",
language = "English",
volume = "80",
pages = "460--465.e9",
journal = "American Academy of Dermatology. Journal",
issn = "0190-9622",
publisher = "Mosby, Inc.",
number = "2",

}

Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors : A nationwide case-control study. / Pedersen, Sidsel Arnspang; Johannesdottir Schmidt, Sigrun Alba; Hölmich, Lisbet Rosenkrantz; Friis, Søren; Pottegård, Anton; Gaist, David.

In: Journal of the American Academy of Dermatology, Vol. 80, No. 2, 02.2019, p. 460-465.e9.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors

T2 - A nationwide case-control study

AU - Pedersen, Sidsel Arnspang

AU - Johannesdottir Schmidt, Sigrun Alba

AU - Hölmich, Lisbet Rosenkrantz

AU - Friis, Søren

AU - Pottegård, Anton

AU - Gaist, David

N1 - Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

PY - 2019/2

Y1 - 2019/2

N2 - Background: 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). Objective: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. Methods: 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. Results: 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). Limitations: No data on sun exposure was available. Conclusion: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.

AB - Background: 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). Objective: To examine the association between hydrochlorothiazide use and the risk for MCC and MAST. Methods: 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. Results: 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). Limitations: No data on sun exposure was available. Conclusion: Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.

KW - Merkel cell carcinoma

KW - antihypertensives

KW - epidemiology

KW - hydrochlorothiazide

KW - malignant adnexal skin tumors

KW - pharmacology

KW - skin cancer

KW - Multivariate Analysis

KW - Age Distribution

KW - Prognosis

KW - Humans

KW - Middle Aged

KW - Male

KW - Skin Neoplasms/chemically induced

KW - Case-Control Studies

KW - Incidence

KW - Dose-Response Relationship, Drug

KW - Carcinoma, Merkel Cell/chemically induced

KW - Aged, 80 and over

KW - Female

KW - Hypertension/diagnosis

KW - Registries

KW - Retrospective Studies

KW - Odds Ratio

KW - Hydrochlorothiazide/adverse effects

KW - Risk Assessment

KW - Logistic Models

KW - Neoplasms, Adnexal and Skin Appendage/chemically induced

KW - Survival Analysis

KW - Denmark

KW - Sex Distribution

KW - Aged

U2 - 10.1016/j.jaad.2018.06.014

DO - 10.1016/j.jaad.2018.06.014

M3 - Journal article

VL - 80

SP - 460-465.e9

JO - American Academy of Dermatology. Journal

JF - American Academy of Dermatology. Journal

SN - 0190-9622

IS - 2

ER -