Lithium may reduce melanoma risk

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.

Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients.

Microarray gene profiling techniques suggest that Wnt genes, which “encode a family of secreted glycoproteins that activate cellular signaling pathways to control cell differentiation, proliferation, and motility,” may be involved in melanoma development, wrote Maryam M. Asgari, MD, of the department of dermatology at Massachusetts General Hospital and the department of population medicine at Harvard University, both in Boston, and her colleagues. In particular, “transcriptional profiling of melanoma cell lines has suggested that Wnt/beta-catenin signaling regulates a transcriptional signature predictive of less aggressive melanoma,” they wrote.

The psychiatric medication lithium activates the Wnt/beta-catenin signaling pathway and has shown an ability to inhibit the proliferation of melanoma cells in a mouse model, but “to our knowledge, no published epidemiologic studies have examined the association of melanoma risk with lithium exposure,” they wrote.

The researchers reviewed data from the Kaiser Permanente Northern California database of 2,213,848 adult white patients who were members during 1997-2012, which included 11,317 with lithium exposure. They evaluated the association between lithium exposure and both incident melanoma risk and melanoma-associated mortality (J Invest Dermatol. 2017 Oct;137[10]:2087-91.).

Individuals exposed to lithium had a 32% reduced risk of melanoma in an unadjusted analysis; in an adjusted analysis, the reduced risk was 23% and was not significant.

However, there was a significant difference in melanoma incidence per 100,000 person-years in lithium-exposed individuals, compared with unexposed individuals (67.4 vs. 92.5, respectively; P = .027).

Among patients with melanoma, those with exposure to lithium had a lower mortality rate than those not exposed (4.68 vs. 7.21 per 1,000 person-years, respectively), but the sample size for this subgroup was too small to determine statistical significance. In addition, lithium exposure was associated with reduced likelihood of developing skin tumors greater than 4 mm and of presenting with extensive disease. Among those exposed to lithium, none presented with a thick tumor (Breslow depth greater than 4 mm), and none had regional or distant disease when they were diagnosed, compared with 2.8% and 6.3%, respectively, of those not exposed to lithium.

The findings were limited by several factors, including reliance on prescription information to determine lithium exposure, a homogeneous study population, and confounding variables, such as sun exposure behaviors, the researchers noted. However, the large study population adds strength to the results, and “our conclusions provide evidence that lithium, a relatively inexpensive and readily available drug, warrants further study in melanoma,” they said.

Lead author Dr. Asgari and one of the other four authors disclosed serving as investigators for studies funded by Valeant Pharmaceuticals and Pfizer. This study was supported by the National Cancer Institute. Dr. Asgari is principal investigator in the Patient-Oriented Research in the Epidemiology of Skin Diseases lab at Massachusetts General Hospital, Boston.