Department of Dermatology, Massachusetts General Hospital, and Department of Population Medicine, Harvard Medical School, Boston, Massachusetts, USA; Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Division of Dermatology, University of Washington Medical Center, Seattle, Washington, USA; The Group Health Research Institute, Seattle, Washington, USA.
J Invest Dermatol. 2017 Oct;137(10):2087-2091. doi: 10.1016/j.jid.2017.06.002. Epub 2017 Jun 17.
Laboratory studies show that lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but to our knowledge no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n = 2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n = 11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n = 14,056) were identified from an established cancer registry. In addition to examining melanoma incidence, melanoma hazard ratios and 95% confidence intervals for lithium exposure were estimated using Cox proportional hazards models, adjusted for potential confounders. Melanoma incidence per 100,000 person-years among lithium-exposed individuals was 67.4, compared with 92.5 in unexposed individuals (P = 0.027). Lithium-exposed individuals had a 32% lower risk of melanoma (hazard ratio = 0.68, 95% confidence interval = 0.51-0.90) in unadjusted analysis, but the estimate was attenuated and nonsignificant in adjusted analysis (adjusted hazard ratio = 0.77, 95% confidence interval = 0.58-1.02). No lithium-exposed individuals presented with thick (>4 mm) or advanced-stage melanoma at diagnosis. Among melanoma patients, lithium-exposed individuals were less likely to suffer melanoma-associated mortality (rate = 4.68/1,000 person-years) compared with the unexposed (rate = 7.21/1,000 person-years). Our findings suggest that lithium may reduce melanoma risk and associated mortality.
实验室研究表明，激活 Wnt/β-连环蛋白信号通路的锂可减缓黑色素瘤的进展，但据我们所知，尚未有发表的流行病学研究探讨过这种关联。我们开展了一项回顾性队列研究，纳入了 1997 年至 2012 年期间的成年白人 Kaiser Permanente Northern California 会员（n=2213848），以检验锂的使用与黑色素瘤风险之间的关联。从药房数据库评估锂暴露情况，从电子实验室数据库获取血清锂水平，从已建立的癌症登记处确定新发皮肤黑色素瘤（n=14056）。除了检查黑色素瘤发病率之外，还使用 Cox 比例风险模型估计了锂暴露的黑色素瘤风险比和 95%置信区间，模型调整了潜在混杂因素。暴露于锂的个体中每 100000 人年的黑色素瘤发病率为 67.4，而未暴露个体的发病率为 92.5（P=0.027）。在未调整分析中，锂暴露个体的黑色素瘤风险降低了 32%（风险比=0.68，95%置信区间=0.51-0.90），但在调整分析中，该估计值减弱且不显著（调整后的风险比=0.77，95%置信区间=0.58-1.02）。在诊断时，没有锂暴露的个体表现出厚（>4mm）或晚期黑色素瘤。在黑色素瘤患者中，与未暴露个体（发生率=7.21/1000 人年）相比，锂暴露个体的黑色素瘤相关死亡率较低（发生率=4.68/1000 人年）。我们的研究结果表明，锂可能降低黑色素瘤风险和相关死亡率。
