CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma.,Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype.,All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL).,Phenotypic data related to primary melanoma and pigmentation characteristics were collected.,The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced.,Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation.,The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years.,Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM).,A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects.,CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001).,MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010).,Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM.,In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation.
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.