Laboratory studies show lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but 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 (HRs) and 95% confidence intervals (CIs) 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 to 92.5 in unexposed individuals (p = 0.027). Lithium-exposed individuals had a 32% lower risk of melanoma risk (HR=0.68; CI 0.51-0.90) in unadjusted analysis, but the estimate was attenuated and non-significant in adjusted analysis (aHR=0.77; CI 0.58-1.02). No lithium-exposed individuals presented with thick (> 4 mm) or advanced-stage melanoma at diagnosis. Among melanoma cases, lithium-exposed individuals were less likely to suffer melanoma-associated mortality (rate = 4.68/1,000 person years) as compared to the unexposed (rate = 7.21/1,000 person-years). Our findings suggest lithium may reduce melanoma risk and associated mortality.
J. Invest. Dermatol.
Association between lithium use and melanoma risk and mortality: A population-based study.