Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses

BACKGROUND: Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. OBJECTIVE: The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. METHODS: We searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I(2) metric), evidence for small-study effects and excess significance bias. RESULTS: Forty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at P