Sunscreen Use and the Risk for Melanoma: A Quantitative Review

Context Reports that sunscreen use increases risks for melanoma have led to controversy. Contribution This meta-analysis of 18 casecontrol studies found no good evidence for an increased risk for melanoma with sunscreen use. Several studies did not account for patients' sensitivity to sunlight, which could increase both sunscreen use and melanoma. A few studies found protective relationships between sunscreen use and melanoma. Implications Previous reports of increased risk for melanoma with sunscreen use were misleading. Cautions Studies that were reviewed did not evaluate newer sunscreens with a sun protection factor greater than 15, protection against ultraviolet A radiation, or water resistance. The Editors In 2003, an estimated 54200 cases (29900 in men and 24300 in women) of melanoma will be diagnosed in the United States, and 7600 people (4700 men and 2900 women) will have died of melanoma (1). The incidence of skin melanoma is increasing faster than that of any other type of cancer in the United States (2). The age-adjusted incidence of melanoma reported by the Surveillance Epidemiology and End Results (SEER) registries increased from 7.4 per 100000 persons in 1973 to 20.1 per 100000 in 1999 among white persons (3). Melanoma occurs predominantly in white persons, and its incidence increases with age. The 2 major etiologic risk factors for melanoma are sun sensitivity (tendency to burn, inability to tan, light skin color, or tendency to develop freckles) and exposure to ultraviolet radiation through sun exposure. Additional risk factors include age, sex, family history of melanoma, many nevi, and possible exposure to artificial ultraviolet radiation (through tanning beds). Various other factors have also been examined, including oral contraceptive use, diet, smoking, and alcohol use, but no consistent associations have been established. Sunscreens are thought to protect skin from many of the harmful effects of the sun. Consequently, some professionals suggest that limiting exposure to ultraviolet radiation through use of sunscreen during childhood can reduce the lifetime risk for nonmelanoma skin cancers by as much as 78% (4). In contrast, several recent reports (5-8) have suggested that sunscreen use may cause melanoma. Sun sensitivity probably positively confounds the association between sunscreen use and melanoma, yet few studies have stratified participants by sun sensitivity or appropriately controlled for this factor. We sought to examine the strength and the consistency of the observed associations between melanoma and sunscreen use. Where possible, we examined sunscreen use stratified by sun sensitivity. Methods Literature Search To identify relevant studies for sunscreen use and melanoma, we searched the MEDLINE database by using melanoma (epidemiology or etiology) and sunscreening agents as Medical Subject Headings and melanoma and sunscreen as key words or text words. The search was repeated periodically to account for fluctuations in the results of searches. We also searched Cancerlit but found no additional articles. We checked the references of identified articles, including bibliographies of the review articles, for additional relevant studies. We also reviewed 70 articles from the first author's files that appeared to be related to melanoma and sunscreen use, sunburns, or sunlight. Only cohort and casecontrol studies that measured sunscreen use in relation to melanoma were included. Of the eligible articles, 6 were not in the English language. These were reviewed by 1 person who was multilingual and trained in epidemiology; however, none reported on sunscreen use. In May 2003, the MEDLINE search for articles published from 1966 through April 2003 was repeated by using melanoma (epidemiology or etiology) and sunscreening agents as Medical Subject Headings and melanoma and sunscreen as key words or text words (Figure 1). The latter search found 138 articles, including 14 casecontrol studies; 32 review articles on melanoma; 42 editorials or commentaries; 4 articles on melanoma trends; 41 articles on habits, behaviors, or prevention; 4 prevention trials that did not examine melanoma as an outcome; and 1 animal study. Of the 14 casecontrol studies found, 12 had relevant data. Figure 1. Literature search for articles on risk for melanoma and sunscreen use. We then expanded our MEDLINE search to include melanoma and sunburns as Medical Subject Headings, key words, and text words, in an attempt to find additional studies not listed on key or text words for sunscreen. Of 183 articles found through this expanded search, we reviewed 67 in detail, which yielded 6 additional articles on sunscreen use. Three additional articles not found on MEDLINE were obtained from authors' files; 2 of these articles were also discussed in other reviews. Among 3 review articles, 17 studies were discussed, of which 13 were found on MEDLINE, 2 were found in the authors' files, and 2 were not found elsewhere. Two additional studies, 1 of which was an abstract and 1 an unpublished study, were found in the references of reviews on sunscreen use (9, 10) but not on MEDLINE. The authors were contacted but provided no additional data. In general, authors were not contacted because the response rate was low in a previous meta-analysis. Of the 23 relevant analytic articles on sunscreen use and melanoma, 3 were duplicate publications, leaving 20 independent studies. One of the 20 studies reported only on tanning lotion. Selection Criteria Cohort, casecontrol, and cross-sectional studies that included adults or children were considered for this meta-analysis. However, we found no cohort or cross-sectional studies of sunscreen use and development of melanoma. One author and an assistant screened the titles and abstracts obtained from the literature review to exclude case reports; commentaries; and articles on melanoma trends, habits and behaviors, and other biological aspects of melanoma. If relevance was unclear, the study was reviewed in detail by 2 independent reviewers. Studies that reported use of what appeared to be tanning oils or tanning enhancers rather than sunscreen were independently reviewed and were later excluded from pooled analyses. We included studies that reported odds ratios and those that reported the percentage of cases and controls who used sunscreen. Because the diagnosis of melanoma is based on histologic examination, all studies were assumed to have included histologic confirmation, even if this was not explicitly stated. Data Extraction For each study and level of sunscreen use, the natural log of the odds ratio and its variance were required. Where available, the variances were calculated on the basis of the reported CIs (11). Otherwise, we calculated the variances of the natural log of the odds ratio from reported data. For studies that reported no association between melanoma and sunscreen and did not report an odds ratio, we assumed an estimated odds ratio of 1.0. We estimated corresponding variances on the basis of the number of participants, assuming an average exposure rate that was calculated from all other studies. When available, covariate-adjusted odds ratios were used. Reviewers were blinded to the authors, journal of publication, and introduction and discussion of each article. Two independent reviewers abstracted data from every article, and the 2 sets of results were compared for concordance and rereviewed if necessary. Inconsistencies were rereviewed until agreement was achieved. We sought third-party resolution of disagreements when necessary. We classified studies as hospital-based if they used hospital, clinic, or unidentified control groups. We considered studies that included neighborhood controls, community controls, and general populationbased controls to be population based. The most adjusted odds ratios were abstracted, and we assumed that the authors had properly examined and adjusted for confounders. Because of heterogeneity, we examined subgroups of studies that reported adjustment for sun sensitivity, sunburns, and other sun exposure. Study Quality On the basis of our previous study of melanoma and meta-analyses, we developed a quality-assessment scoring system for articles reporting on melanoma and sunscreen use. Two reviewers applied the system to each of the 20 studies. Because selection of the control group is pertinent, we scored studies as follows: hospital, cancer, or outpatient dermatology controls, 0 points; hospital visitors, or other unclear group, 1 point; and population controls, 2 points. Studies were given credit for standardizing or pretesting the questionnaire in a sample similar to their study sample (2 points) or partial credit for using the same questions from a structured questionnaire (1 point). Interviewer-administered studies were assigned a score of 2 points if the interviewer was blinded to the status of the patient and 1 point if he or she was not blinded; studies in which questionnaires were self-administered were assigned a score of 0 points. To help account for potential detection bias, we gave credit to studies in which the control group had a skin examination (1 point). To address the potential confounding of sun sensitivity in the relationship between sunscreen and melanoma, we assigned several scores according to the method by which sun sensitivity was measured. A higher score was given to studies that adjusted for skin color, skin type, ability to tan, and tendency to burn (4 points), whereas a lower score was assigned to those that adjusted only for hair color, eye color, or freckling (2 points). We gave credit to studies that adjusted for the potential confounders of sunburn (2 points) and other sun exposure (2 points) and to those that partially adjusted for these confounders (1 point). In addition, points were assigned to studies that adjusted or matched for sex and age (2 points) or were frequency-matched only (1 point). In examining