西班牙一项大型巢式病例对照研究中氢氯噻嗪的使用与皮肤癌风险
Use of hydrochlorothiazide and risk of skin cancer in a large nested case-control study in Spain.
作者信息
León-Muñoz Luz M, Duarte-Salles Talita, Llorente Ana, Díaz Yesika, Puente Diana, Pottegård Anton, Montero-Corominas Dolores, Huerta Consuelo
机构信息
División de Farmacoepidemiología y Farmacovigilancia. Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios (AEMPS).
Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
出版信息
Pharmacoepidemiol Drug Saf. 2021 Sep;30(9):1269-1278. doi: 10.1002/pds.5295. Epub 2021 Jun 8.
PURPOSE
Hydrochlorothiazide (HCTZ) use has been linked to skin cancer in northern European countries. We assessed the association between HCTZ exposure and risk of malignant melanoma (MM) and keratinocyte carcinoma (KC) in a European Mediterranean population.
METHODS
Two parallel nested case-control studies were conducted in Spain using two electronic primary healthcare databases, each one providing data on both exposure and outcomes: SIDIAP and BIFAP. Cancer cases were matched to 10 controls by age and gender through risk-set sampling. The ORs and 95% CI for MM and KC associated with previous HCTZ use were estimated using conditional logistic regression. In BIFAP, KC cases were further identified as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC).
RESULTS
In adjusted analyses, both ever and cumulative high (≥50,000 mg) use of HCTZ were associated with an increased risk of KC. The risk estimates for high use were 1.30 (1.26-1.34) in SIDIAP and 1.20 (1.12-1.30) in BIFAP, with a lower risk for BCC (1.11 [1.02-1.21]) than for SCC (1.71 [1.45-2.02]). A dose-response relationship was observed between cumulative doses of HCTZ and KC risk. Inconsistent results were found for high use of HCTZ and risk of MM: 1.25 (1.09-1.43) in SIDIAP and 0.85 (0.64-1.13) in BIFAP.
CONCLUSIONS
In this European Mediterranean population, a high cumulative use of HCTZ was related to an increased risk of KC with a clear dose-response pattern.
目的
在北欧国家，氢氯噻嗪（HCTZ）的使用与皮肤癌有关。我们评估了欧洲地中海人群中HCTZ暴露与恶性黑色素瘤（MM）和角质形成细胞癌（KC）风险之间的关联。
方法
在西班牙利用两个电子初级医疗保健数据库进行了两项平行的巢式病例对照研究，每个数据库都提供暴露和结局数据：SIDIAP和BIFAP。通过风险集抽样，将癌症病例按年龄和性别与10名对照进行匹配。使用条件逻辑回归估计与先前使用HCTZ相关的MM和KC的比值比（OR）及95%可信区间（CI）。在BIFAP中，KC病例进一步分为基底细胞癌（BCC）或鳞状细胞癌（SCC）。
结果
在调整分析中，曾经使用HCTZ以及累积高剂量（≥50,000毫克）使用HCTZ均与KC风险增加相关。在SIDIAP中，高剂量使用的风险估计值为1.30（1.26 - 1.34），在BIFAP中为1.20（1.12 - 1.30），BCC的风险（1.11 [1.02 - 1.21]）低于SCC（1.71 [1.45 - 2.02]）。观察到HCTZ累积剂量与KC风险之间存在剂量反应关系。关于高剂量使用HCTZ与MM风险的结果不一致：在SIDIAP中为1.25（1.09 - 1.43），在BIFAP中为0.85（0.64 - 1.13）。
结论
在这个欧洲地中海人群中，高累积使用HCTZ与KC风险增加相关，且呈现明确的剂量反应模式。
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