In this paper, we report baseline results of the first known population-based, prospective study of nevi in a US cohort of children that documents the natural history of nevi using digital photography and assesses associations of phenotype, sun-exposure, and sun-protective behaviors with the prevalence and progression of nevi over a 4-year follow-up. Our results pertain to baseline findings and predictors of nevus count at the completion of year 1 data collection.
The study was conducted among children and their parents from the Framingham, Massachusetts, school system. This site was chosen because it provides a natural setting for long-term observational studies of children. Specifically, the school system 1) offers a cohort with a racial/ethnic mix similar to that of the US population (in the cohort, 70.0% of the children are white, 20.5% are nonwhite Hispanic, 4.3% are black/African American, and 5.2% are Asian American and other; the 2000 US census estimated that 63% of children aged 10–14 years are white, 17% are nonwhite Hispanic, 16% are black/African American, and 4% are Asian American and other) (42
); 2) has successfully participated in large-scale health studies including a pilot of this study (38
); and 3) has an excellent infrastructure for performing annual scoliosis examinations, which was crucial to implementing this study (36
In our study, male students had 38% more nevi than females did. Other studies have suggested that male children have more nevi than female children (15
). In an analysis of nevi in 2,552 Australian schoolchildren aged 5–14 years, males had more nevi at all ages than did females; median total-body nevus counts ranged from 40 at 5 years of age to 96 at 14 years of age in females, and from 51 to 120 in males, respectively (15
). The results of our study show that total nevus count is associated with skin and hair color and tendency to burn, as measured by an index for sun sensitivity (SSI). Students with dark skin, dark hair, and no tendency to burn were less likely to have nevi. We also observed a small group of students with light skin, light hair, and tendency to burn who had few nevi. The presence of back freckling was also positively associated with nevus count. These findings are consistent with those of previous longitudinal and cross-sectional studies (13
In multivariate analyses, male gender, hours spent in the sun, number of painful sunburns, wearing a shirt or hat, back freckling, and SSI were associated with increased number of nevi. Hours spent in the sun, as a measure of cumulative sun exposure, was associated with an increased number of nevi. This finding is in agreement with other studies (16, 33, 48). Results from previous studies on painful sunburning have shown inconsistent results, with some studies reporting a positive association while others not demonstrating this effect (13
We assessed sun-protective behaviors, including using sunscreen and wearing protective clothing. Our results for wearing protective clothing were unexpected and are contradictory to those from other studies in which children with high nevus counts were less likely to practice sun-protective behaviors. It is possible that children's T-shirts worn at the beach do not protect enough against ultraviolet rays when exposed to intense sun or that the shirts do not protect all of the skin, or both, thus exposing children to burns and possibly new moles. In a study by English et al. (16
), children whose backs were covered least often when outdoors had the most nevi. In other studies (33
), wearing clothing has been associated with fewer nevi. In our study, sunscreen use was interrogated with multiple questionnaire items including use of sunscreen on the face and back when outdoors and by the pool or beach. We elected to include sunscreen use in the multivariate model because of its hypothesized role as a protective factor against nevus counts. However, none of the sunscreen items were significantly associated with total back nevus counts. The rate ratio estimates of the significant risk factors did not change appreciably regardless of which sunscreen item was included in the multivariate model.
illustrates the multivariate model including sunscreen use on the back when outdoors. Studies have been inconclusive, with a single randomized trial showing evidence of benefit and the prevention of nevi (20
), while other studies have shown a positive association between sunscreen use and nevus count (26
). It has been proposed that these discrepant findings are due to confounding and/or measurement error. Male gender was associated with increased nevus count, after adjustment for potential confounding factors, which is consistent with other studies in which investigators have observed a higher number and density of nevi (13
This analysis was cross-sectional and thus has inherent limitations related to the temporal sequence of exposures and outcome. The longitudinal design of this study will enable future analyses to assess risk factors for the development of incident nevi and address the temporal relation between exposures and nevus phenotype. This study was limited to nevi on the back as the anatomic focus. Selection of the back was based on both logistic and epidemiologic considerations (11
). The existing school infrastructure for administering scoliosis examinations, along with the efficiency of restricting the study to the skin of the back, was anticipated to result in very high participation rates and excellent data quality, as demonstrated in our pilot study (38
Other logistic considerations in selecting the back were its relatively flat surface, which lends itself to photography studies. The utility and efficiency of restricting our study to the back are supported by several epidemiologic studies: English et al. (15
) demonstrated the least interobserver variation for nevus counts of the back relative to other anatomic sites, as well as excellent correlation between back nevus counts from photographs and those from direct examination. Autier et al. (11
) demonstrated a strong correlation between back and total nevus counts and recognized the phenotype of back nevi as an excellent marker of melanoma risk. Uncontrolled confounding is also a potential source of error in this study related to factors associated with sun exposure, sun protection, and nevus phenotype. The potential for misclassification of important factors such as SSI is small because students underwent a brief visual examination to assess hair, eye, and skin color by a trained nurse, and tendency to burn was obtained by student self-report. Furthermore, these data were collected without knowledge of the outcome of interest, log mole count. Mole count was assessed without knowledge of the potential predictor variables.
Understanding the cause and development of nevi has important public health implications for primary and secondary prevention of melanoma. Public health campaigns and clinical efforts to reduce melanoma deaths currently target individuals with many nevi or apparently atypical nevi. Melanoma is very uncommon in early life, representing 1%–3% of all malignant tumors in people younger than 20 years of age (59
). Despite this rarity, recent evidence has indicated that melanoma is now occurring more frequently in children and adolescents (59
). The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute reported the incidence of malignant melanoma in children to be 1.3 per 1 million (72
). The incidence of melanoma in children (aged <20 years) increased 2.9% (95% confidence interval: 2.1, 3.6) per year from 1973 to 2001 (70
). However, the incidence of melanoma among children did not grow more than the incidence among people of other ages during this same time period. In fact, the 2.9% increase is consistent with the annual percentage increase found for persons of all ages in the same period.
Greater public and clinician attention to signs of early melanoma in persons of all ages is one important factor that contributes to this finding. Identification of factors that predict the development of multiple and atypical nevi will improve targeting of primary and secondary prevention efforts in early life. Because these factors may be apparent earlier in life, there is an opportunity to intervene when sun-protection efforts are more likely to succeed. With regard to secondary prevention of melanoma, recent efforts at early detection have intensified across all age groups, with an emphasis on the importance of change in a nevus as a sensitive marker of early curable disease. This emphasis has led to increasing nevus biopsies in adolescence. Understanding nevus evolution is critical to avoiding unnecessary biopsies in this age group.
In conclusion, results of our study suggest that numerous factors, both constitutional and environmental, affect nevus count. It is important to understand the heterogeneity of the relation between these factors and nevus phenotype. Assessment of the impact of sun-protective behaviors requires better measures and improved strategies for control of confounding. Future analyses based on the longitudinal data from this study will provide the opportunity to shed light on these important associations.