磷酸二酯酶 5 抑制剂与黑色素瘤皮肤癌风险。

Phosphodiesterase Type 5 Inhibitors and the Risk of Melanoma Skin Cancer.

机构信息

Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.

Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.

出版信息

Eur Urol. 2016 Nov;70(5):808-815. doi: 10.1016/j.eururo.2016.04.035. Epub 2016 May 10.

DOI:10.1016/j.eururo.2016.04.035

PMID:27178449

Abstract

BACKGROUND

The association between phosphodiesterase type 5 inhibitors (PDE5-Is), drugs used in the treatment of erectile dysfunction (ED), and melanoma skin cancer is controversial.

OBJECTIVE

To assess whether the use of PDE5-Is is associated with an increased risk of melanoma skin cancer.

DESIGN, SETTING, AND PARTICIPANTS: Using the UK Clinical Practice Research Datalink, we assembled a cohort of men newly diagnosed with ED between 1998 and 2014 and followed until 2015. PDE5-I exposure was considered as a time-varying variable lagged by 1 yr for latency purposes.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident melanoma associated with PDE5-I use overall and by number of prescriptions and pills received. Identical analyses were conducted for basal and squamous cell carcinoma, two cancers for which PDE5-related pathways are not thought to be involved.

RESULTS AND LIMITATIONS

The cohort included 142 983 patients, of whom 440 were newly diagnosed with melanoma during follow-up (rate: 63.0 per 100 000 person-years). Compared with nonuse, PDE5-I use was not associated with an overall increased risk of melanoma (rates: 66.7 vs 54.1 per 100 000 person-years; HR: 1.18; 95% CI, 0.95-1.47). The risk was significantly increased among those who had received seven or more prescriptions and ≥25 pills (HR: 1.30 [95% CI, 1.01-1.69] and 1.34 [95% CI, 1.04-1.72], respectively). In contrast, there was no overall association with basal and squamous cell carcinoma, with an unclear association with numbers of prescriptions and pills received.

CONCLUSIONS

The use of PDE5-Is was not associated with an overall increased risk of melanoma skin cancer. The increased risks observed in the highest prescription and pill categories require further validation.

PATIENT SUMMARY

In this study, the use of phosphodiesterase type 5 inhibitors was not associated with an increased risk of melanoma skin cancer.

摘要

背景

磷酸二酯酶 5 抑制剂（PDE5-Is）与黑色素瘤皮肤癌之间的关联存在争议，此类药物被用于治疗勃起功能障碍（ED）。

目的

评估 PDE5-Is 的使用是否与黑色素瘤皮肤癌风险的增加相关。

设计、设置和参与者：我们使用英国临床实践研究数据链接，组建了一个于 1998 年至 2014 年间新诊断为 ED 的男性队列，并随访至 2015 年。PDE5-I 暴露被视为一个时变变量，潜伏期滞后 1 年。

结局测量和统计分析

使用 Cox 比例风险模型，估计了 PDE5-I 使用与黑色素瘤发病风险的相关性，总体风险比（HR）及其 95%置信区间（CI），并按处方和药丸数量进行分层。针对基底细胞癌和鳞状细胞癌（这两种癌症被认为与 PDE5 相关途径无关）进行了相同的分析。

结果和局限性

该队列包括 142983 名患者，其中 440 名在随访期间被新诊断为黑色素瘤（发生率：63.0/100000 人年）。与不使用相比，PDE5-I 使用与黑色素瘤总体风险的增加无关（发生率：66.7 比 54.1/100000 人年；HR：1.18；95%CI，0.95-1.47）。在接受 7 次或更多处方和≥25 片药丸的患者中，风险显著增加（HR：1.30[95%CI，1.01-1.69]和 1.34[95%CI，1.04-1.72]）。相比之下，PDE5-Is 使用与基底细胞癌和鳞状细胞癌总体风险无关，与处方和药丸数量的关联不明确。