Abstract:
Background: A previous study in Denmark suggested an increased melanoma risk associated with the use of flecainide. Objective: To study the association between flecainide use and the risk of melanoma and non-melanoma skin cancer in Spain and Denmark. Methods: We conducted a multi-database case-control study in (database/study period) Spain (SIDIAP/2005-2017 and BIFAP/2007-2017) and Denmark (Danish registries/2001-2018). We included incident cases of melanoma or non-melanoma skin cancer (NMSC) aged ≥18 with ≥2 years of previous data (≥10 years for Denmark) before the skin cancer and matched them to controls (10:1 by age and sex). We excluded persons with immunosuppression or previous cancer. We defined ever-use as any prescription fill and high-use as a cumulative dose of at least 200 g (reference: never-use). We categorized a cumulative dose for a dose-response assessment. We used conditional logistic regression to compute ORs (95% CI) adjusted for photosensitizing, anti-neoplastic, disease-specific drugs and comorbidities. Results: The total numbers of melanoma/NMSC cases included were 7,809/64,230 in SIDIAP, 4,661/31,063 in BIFAP, and 27,978/152,821 in Denmark. In Denmark, high-use of flecainide was associated with increased adjusted ORs of skin cancer compared with never-use [melanoma: OR 1.97 (1.38-2.81); NMSC: OR 1.34 (1.15-1.56)]. In Spain, an association between high-use of flecainide and NMSC was also observed [BIFAP: OR 1.42 (1.04-1.93); SIDIAP: OR 1.19 (0.95-1.48)]. There was a non-significant dose-response pattern for melanoma in Denmark and no apparent dose-response pattern for NMSC in any of the three databases. We found similar results for ever-use of flecainide. Conclusion: Flecainide use was associated with an increased risk of melanoma (Denmark only) and NMSC (Denmark and Spain) but without substantial evidence of dose-response patterns. Further studies are needed to assess for possible unmeasured confounders.
摘要:
背景:丹麦先前的一项研究表明,与使用氟卡尼相关的黑色素瘤风险增加。目的:研究西班牙和丹麦使用氟卡尼与黑色素瘤和非黑色素瘤皮肤癌风险之间的关系。方法:我们在(数据库/研究期间)西班牙(SIDIAP/2005-2017和BIFAP/2007-2017)和丹麦(丹麦注册/2001-2018)进行了多数据库病例对照研究。我们纳入了年龄≥18岁的黑色素瘤或非黑色素瘤皮肤癌(NMSC)的偶发病例,其中既往数据≥2年(丹麦≥10年),并将其与对照组相匹配(按年龄和性别10:1)。我们排除了免疫抑制患者或既往癌症患者。我们将使用任何处方填充和高使用定义为至少200克的累积剂量(参考:从未使用)。我们对累积剂量进行了分类,以进行剂量反应评估。我们使用条件逻辑回归来计算针对光敏化调整的OR(95%CI),抗肿瘤,疾病特异性药物和合并症。结果:SIDIAP中包括的黑色素瘤/NMSC病例总数为7,809/64,230,4,661/31,063在BIFAP,和27,978/152,821在丹麦。在丹麦,与从未使用相比,氟卡尼的大量使用与皮肤癌的校正OR增加相关[黑色素瘤:OR1.97(1.38~2.81);NMSC:OR1.34(1.15~1.56)].在西班牙,还观察到大量使用氟卡尼和NMSC之间存在关联[BIFAP:OR1.42(1.04~1.93);SIDIAP:OR1.19(0.95~1.48)].在丹麦,黑素瘤存在非显著的剂量-反应模式,而在三个数据库中的任何一个中,NMSC没有明显的剂量-反应模式。我们发现使用氟卡尼的结果相似。结论:氟卡尼的使用与黑色素瘤(仅限丹麦)和NMSC(丹麦和西班牙)的风险增加相关,但没有剂量反应模式的实质性证据。需要进一步的研究来评估可能无法测量的混杂因素。