Challenges in assessing the sunscreen-melanoma association

Abstract

Whether sunscreen use affects melanoma risk has been widely studied with contradictory results. To answer this question we performed a systematic review of all published studies, accounting for sources of heterogeneity and bias. We searched for original articles investigating the sunscreen-melanoma association in humans to February 28, 2018. We then used random-effects meta-analysis to combine estimates of the association, stratified by study design. Stratified meta-analysis and meta-regression were used to identify sources of heterogeneity. We included 21,069 melanoma cases from 28 studies published 1979-2018: 23 case-control (11 hospital-based, 12 population-based), 1 ecological, 3 cohort and 1 randomised controlled trial (RCT). There was marked heterogeneity across study designs and among case-control studies but adjustment for confounding by sun exposure, sunburns and phenotype systematically moved estimates toward decreased melanoma risk among sunscreen users. Ever- vs. never-use of sunscreen was inversely associated with melanoma in hospital-based case-control studies (adjusted odds ratio (OR) = 0.57, 95%confidence interval (CI) 0.37-0.87, p_{heterogeneity} < 0.001), the ecological study (rate ratio = 0.48, 95%CI 0.35-0.66), and the RCT (hazard ratio (HR) = 0.49, 95%CI 0.24-1.01). It was not associated in population-based case-control studies (OR = 1.17, 95%CI 0.90-1.51, p_{heterogeneity} < 0.001) and was positively associated in the cohort studies (HR = 1.27, 95%CI 1.07-1.51, p_{heterogeneity} = 0.236). The association differed by latitude (p_interaction = 0.042), region (p_interaction = 0.008), adjustment for naevi/freckling (p_interaction = 0.035), and proportion of never-sunscreen-users (p_interaction = 0·012). Evidence from observational studies on sunscreen use and melanoma risk was weak and heterogeneous, consistent with the challenges of controlling for innate confounding by indication. The only RCT showed a protective effect of sunscreen.

Keywords: melanoma; meta-analysis; skin cancer; sun protection; sunscreen.

Figure 1

Flow diagram on inclusion of studies. The figure shows the process of selecting eligible studies for the current review and meta‐analysis. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Forest plot for ever‐ vs. never‐use of sunscreen and melanoma risk, minimally adjusted estimates stratified by study design. The figure shows the forest plot for melanoma risk comparing ever‐ vs. never‐use of sunscreen for all studies that reported a minimally adjusted estimate, stratified by study design. The estimates of the case–control studies are reported in odds ratios with 95% confidence intervals (CIs); and, the estimates of the cohort studies and the RCT as hazard ratios with 95% CIs. Minimal adjustment of some estimates (e.g. age and sex) and exact definition of the estimates is described in Table 2. Abbreviations: CI, confidence interval; ES, effect size; RCT, randomised controlled trial. * Not ever‐ vs. never‐use of sunscreen; see Table 2 for the exact definition of the estimate. **Case‐cohort study. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Forest plot for ever‐ vs. never‐use of sunscreen and melanoma risk, maximally adjusted estimates stratified by study design. The figure shows the forest plot for melanoma risk comparing ever‐ vs. never‐use of sunscreen for all studies that reported a maximally adjusted estimate, stratified by study design. The estimates of the case–control studies are reported as odds ratios with 95% confidence intervals (CIs); the estimates of the cohort studies and the RCT as hazard ratios with 95% CIs; and, the estimate of the ecological study as rate ratio with 95% CI. Adjustment and exact definition of the estimates is described in Table 2. Abbreviations: CI, confidence interval; ES, effect size; RCT, randomised controlled trial. *Not ever‐ vs. never‐use of sunscreen; see Table 2 for the exact definition of the estimate. **Case‐cohort study. [Color figure can be viewed at wileyonlinelibrary.com]