Objective To synthesise the literature on indoor tanning and non-melanoma skin cancer.,Design Systematic review and meta-analysis.,Data sources PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present).,Study selection All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included.,Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English.,Data extraction Two investigators independently extracted data.,Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning.,Dose-response effects and exposure to indoor tanning during early life were also examined.,The population attributable risk fraction for the United States population was calculated.,Results 12 studies with 9328 cases of non-melanoma skin cancer were included.,Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53).,No significant heterogeneity existed between studies.,The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma.,This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning.,On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52).,Conclusions Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer.,The risk is higher with use in early life (<25 years).,This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide.,These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen.
Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment.,We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines.,PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation.,Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM.,Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM.,There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines.,Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines.,However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines.,In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.