The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study

Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2021-11, Vol.30 (11), p.2114-2121
Main Authors: de Haan-Du, Jing, Landman, Gijs W D, Groenier, Klaas H, Vissers, Pauline A J, Louwman, Marieke W J, Kleefstra, Nanne, de Bock, Geertruida H
Format: Article
Language:English
Subjects:
Aged
Carcinoma, Squamous Cell - etiology
Diabetes Mellitus, Type 2 - drug therapy
Diuretics - administration & dosage
Diuretics - adverse effects
Dose-Response Relationship, Drug
Female
Humans
Hydrochlorothiazide - administration & dosage
Hydrochlorothiazide - adverse effects
Male
Middle Aged
Photosensitivity Disorders - chemically induced
Photosensitivity Disorders - complications
Proportional Hazards Models
Prospective Studies
Registries
Skin Neoplasms - etiology
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Summary:Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use. In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.EPI-21-0620