Elsevier

European Journal of Cancer

Volume 46, Issue 13, September 2010, Pages 2467-2472
European Journal of Cancer

High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study

https://doi.org/10.1016/j.ejca.2010.04.024Get rights and content

Abstract

Introduction

In Caucasians, basal cell carcinoma (BCC) is among the most frequently diagnosed cancers and its incidence is increasing. Known risk factors for the development of BCC are age, sun exposure, and certain skin characteristics. Despite photosensitizing abilities of diuretic agents, little is known about a possible association with BCC.

Methods

Data were obtained from the Rotterdam Study; a large prospective population-based follow-up study with coverage of prescription-only drugs from pharmacies. The diagnoses of BCC were obtained through general practitioners, and by linkage with a registry of histo- and cytopathology. Cumulative use of diuretics at the date of diagnosis was categorized into quartiles for users of high-ceiling diuretics, potassium sparing agents and thiazides. The association between these drugs and BCC was assessed by Cox proportional hazard modeling with adjustment for age, gender and potential confounders. Effect modification was tested with interaction terms.

Results

Use of high-ceiling diuretics in the highest quartile (>3.7 years cumulative exposure) was associated with an increased hazard of BCC of 62% compared to no use (HR 1.6; 95% CI 1.1–2.4). Patients who used high-ceiling diuretics and had a high tendency of getting sunburned had a higher risk of diagnosis than non-users who do not easily get sunburned. Neither the use of potassium sparing agents, nor the use of thiazides was associated with BCC.

Conclusion

In our study, cumulative use of high-ceiling diuretics was associated with an increased risk of diagnosis of BCC. This effect is stronger in patients who easily get sunburned.

Introduction

In Caucasians, basal cell carcinoma (BCC) is among the most frequently diagnosed cancers1 and its incidence is increasing.2, 3, 4 In a large region of The Netherlands, the age-adjusted incidence for males rose from 40 per 100,000 person years in 1973 to 92 per 100,000 person years in 2000. For females, the incidence rate rose from 34 to 79 per 100,000 person years during the same period.2 However, mortality rates are low since BCC metastasizes rarely.5, 6 Nonetheless, morbidity can be high due to local tissue destruction, and residual scarring after surgery. Cosmetic considerations and the high incidence make BCC among the five most costly cancers to treat.7

Known risk factors for the development of BCC are age and phenotypic characteristics such as hair color, eye color and skin phototype. In addition to genodermatoses (specific inherited genetic skin conditions), genetic risk factors have been elucidated.8, 9, 10 The major environmental risk factor for the development of BCC is excessive exposure to ultraviolet radiation (UV), both chronic and intermittent.11 UV-B causes specific DNA mutations and UV-A indirectly damages the DNA via reactive oxygen molecules.12, 13, 14 UV induced DNA damage, and therefore the risk of BCC, may be enhanced in patients with increased photosensitivity because they are more likely to get (severe) sunburns due to a lower Minimal Erythema Dose. A wide range of drugs have photosensitizing abilities including sulfonylurea derivatives used in diabetes mellitus, non-steroidal anti-inflammatory drugs, antipsychotic drugs, antimicrobials, antimalarials, amiodarone, diuretics and cardiovascular drugs.15, 16, 17 Of these drugs, amiodarone has been associated with the development of BCC18 and self-reported use of photosensitizing drugs in general was associated with an increased risk of BCC and squamous cell carcinoma (SCC).19 Furthermore, an association between the total dispensed amount of photosensitizing diuretics in mg (i.e. thiazides, potassium sparing agents and furosemide) and risk of SCC and malignant melanoma has been described.20 However, no clear associations were found between diuretics and BCC.

Despite the photosensitizing abilities of diuretic agents, little is known about a possible association between use of these frequently used drugs and the risk of BCC.19, 20 The objective of this study was to test the hypothesis that long-term use of diuretics is associated with an increased risk of BCC.

Section snippets

Setting

Data were obtained from the Rotterdam Study, a large population-based follow-up study. The objectives and design were extensively described earlier.21, 22, 23 In the Rotterdam Study I, 7983 of 10,275 eligible persons aged 55 years and over, participated and are followed since inclusion. They are mainly Caucasians. In 1999, 3011 participants (of 4472 invitees) who had became 55 years of age or older, or moved into the study district since the start of the study were added to the cohort (Rotterdam

Results

We excluded 14 participants from the study population (10,994) who had a diagnosis of BCC and another 288 because they had a prescription for a diuretic before 1st April 1991. The baseline characteristics for the remaining study cohort (10,692) are presented in Table 1. During the period of 1st April 1991 through 31st December 2007, 522 first diagnoses basal cell cancer were made. Of these, 193 patients had drug dispensing data for a diuretic of whom 137 had one or more prescriptions for

Discussion

Although UV exposure is a well-established risk factor for BCC, little is known about the contribution of photosensitizing drugs to BCC development.18, 19, 20, 28 In this study, cumulative exposure time of high-ceiling diuretics was associated with an increased risk of BCC but a significant dose-dependency was not demonstrated. A significantly higher risk of BCC was observed in users of high-ceiling diuretics who tend to get sunburned easily. An explanation could be that the use of high-ceiling

Conflict of interest statement

None of the authors has declared any conflict of interest.

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