Abstract
Introduction
Diuretic thiazides represent a first-line therapeutic option for arterial hypertension. However, this drug class is regarded as having photosensitizing properties, and, as such, may act as a carcinogen, by triggering phototoxic reactions. Whether or not its long-term use increases skin malignancy risk remains unclear.
Purpose
To examine a possible association between thiazide usage and the risk of skin cancer, namely basal cell carcinoma, squamous cell carcinoma and malignant melanoma.
Methods
MEDLINE, EMBASE, Cochrane Library and Google Scholar databases were comprehensively searched, from inception to the first of February of 2019, for observational studies mentioning thiazide diuretic usage and incidence or prevalence of cutaneous basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Literature review, study selection and appraisal, including methodological quality assessment, and data extraction were independently led by two investigators. Meta-analysis was conducted using generic inverse variance outcome and, due to heterogeneity of the original studies, a random effects model. Confounder-adjusted summary relative risk (RR), with 95% confidence interval (CI), was pooled.
Results
Ten studies met eligibility criteria. Of these, six had a case-control design and the remaining were cohort studies. Overall, 7,079,530 patients were included; 125,946 were diagnosed with basal cell carcinoma, 21,775 with squamous cell carcinoma and 31,191 with malignant melanoma. One study encompassed only squamous cell carcinoma of the lip. In five articles, individual thiazides employed were not addressed, whereas three embraced solely hydrochlorothiazide and other two exclusively bendroflumethiazide. Thiazides were found to be associated with increased risk of basal cell carcinoma (six studies, RR=1.05, 95% CI=1.01–1.10, p=0.02, i2=62%), squamous cell carcinoma (seven studies, RR=1.35, 95% CI=1.05–1.74, p=0.02, i2=92%) and malignant melanoma (six studies, RR=1.17, 95% CI 1.11–1.23, p<0.ehz748.03491, i2=0%).
Conclusion
Risk of all three major forms of skin malignancy is heightened in thiazide diuretic users. Increased awareness and education, especially for those who are at high risk and under the form of intense solar irradiation avoidance, are warranted for both patients and healthcare providers.
Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma, and malignant melanoma
