Dataset Information

Associations of thiazide use with skin cancers: a systematic review and meta-analysis.

ABSTRACT:

Background

Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.

Methods

We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use.

Results

We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08-1.24; HR 1.26, 95% CI 1.04-1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06-1.65; HR 1.61, 95% CI 0.97-2.67), and melanoma (OR 1.11, 95% CI 1.02-1.20; HR 1.03, 95% CI 0.93-1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43-4.57; HR 1.20, 95% CI 1.00-1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05-1.33), nodular (OR 1.23, 95% CI 1.08-1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08-1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.

Conclusions

Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.

Trial registration

PROSPERO CRD42021234317 .

SUBMITTER: Shao SC

PROVIDER: S-EPMC9260996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi. METHODS:The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed. RESULTS:Eight RCTs involving 571 patients were included. The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33-0.58, P?<?0.0001) compared to that in the placebo and untreated groups; the pooled RD was -?0.23 (95% CI -?0.30 to -?0.16, P?<?0.0001). The pooled SMD for the 24-h urinary calcium level was -?18.59 (95% CI -?25.11 to -?12.08, P?<?0.0001). The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The subgroup and sensitivity analysis findings were robust. CONCLUSIONS:Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. However, the benefits are insufficient, and the evidence quality is low. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended.