Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study

Abstract

Diuretics have photosensitising properties. However, little is known about how these diuretics affect the risk of skin cancers. In North Jutland County, Denmark, we investigated whether the use of photosensitising diuretics was associated with an increased risk for developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer registry, we identified primary cases of BCC, SCC and MM during the period of 1989 -2003. We selected four population controls for each case from the Danish Civil Registration System, matched on age and gender. Prescriptions for photosensitising diuretics before cancer diagnosis were ascertained in the county's Prescription Database. We used conditional logistic regression to compute incidence rate ratio (IRR), controlling for the chronic medical conditions and for the previous use of oral glucocorticoids. We found an increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45 -2.21)) and MM (IRR of 1.43 (95% CI: 1.09 -1.88)) among users of combined amiloride and hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34 -8.10)) was found among users of indapamide. We found little associations with risk of BCC. Our findings provide evidence that the use of some photosensitising diuretics is associated with an increased risk for SCC and MM.

Known and potential new risk factors for skin cancer in European populations: a multicentre case-control study

“…Possible associations with skin cancer risks were observed with consumption of parsnips (CMM) and with the use of thiazines (BCC), thiazide diuretics (SCC) and cardiac drugs (CMM), as is consistent with the known photosensitizing potential of these food items and drugs. [15][16][17][18][19][20][40][41][42] Of the food and drug associations studied, only a negative association with pomegranate and ciprofloxacin and a positive association with thiazide diuretics remained significant after correction for multiple testing, germane to previously reported association with increased risks of SCC, CMM and BCC. 42,46 When we further analysed the negative association with ciprofloxacin (Table 5), the numbers taking this antibiotic daily for more than 3 months were low (37 controls, 10 BCC, 7 SCC, 12 CMM) and were almost all from Italy, Germany and Poland.…”

“…15,16 Furthermore, in case-control studies reported use of photosensitizing drugs has been associated with increased occurrence of BCC, SCC and actinic keratosis 40,41 and photosensitizing diuretics have been found to associate with increased risks of SCC and CMM. 42 Drug-associated photosensitivity may reflect conversion to electrophiles and ⁄or sources of reactive oxygen species, while other drugs interact synergistically with UV radiation. The immunosuppressant azathioprine, for instance, increases skin sensitivity to UVA by generating 6-thioguanine DNA photoproducts and thus making azathioprine and UVA synergistically mutagenic.…”

“…There are many potential confounders such as use of ciprofloxacin in patients who are sick and less able to lead an active outdoor life. The 'new' variables were investigated based on the hypothesis that they might be related to skin cancer through the biological mechanisms discussed above or because associations have been previously observed, 15,16,18,34,[40][41][42][43]46 but not generally accepted. These associations may be real and deserve further exploration; however, they might also be chance findings.…”

Photosensitizing Medication Use and Risk of Skin Cancer

“…Many drugs, including psoralens, tetracyclines, fluoroquinolones, nonsteroidal anti-inflammatory agents, and amiodarone, are known to have photosensitizing properties (1)(2)(3)(4)(5)(6). There is evidence that photosensitization of the skin followed by exposure to UV radiation (UVR) enhances the risk of sunburns and photo damage to the skin, which might increase the risk of skin cancer (2,5).…”

“…2,7,8) and cutaneous malignant melanoma (CMM) (9). Furthermore, photosensitizing diuretics have been shown to increase the risk of skin malignancies in humans (4), and fluoroquinolone antibiotics have been shown to induce skin lesions (5), SCCs in particular, in mice exposed to UVR (10).…”