Abstract
Background: The incidence of basal cell carcinoma (BCC), which accounts for the majority of non-melanoma skin cancer (NMSC), is increasing, particularly in young people. While BCC is treatable, it can be associated with significant morbidity and health care costs. The ability to identify individuals at the highest risk of early-onset BCC could help focus public health efforts and mitigate the increasing incidence. However, to date, few risk prediction models exist for BCC. To identify individuals at risk of BCC at young ages, we assessed the utility of existing skin cancer risk prediction models (for melanoma or overall skin cancer) in the setting of early-onset BCC and built a novel risk prediction model, with a focus on indoor tanning and melanocortin 1 receptor (MC1R) genotype.
Methods: We evaluated unconditional multivariate logistic regression models among 759 (376 cases, 383 controls) non-Hispanic whites from the Yale Study of Skin Health, a case-control study of early-onset BCC conducted in Connecticut among individuals under age 40. BCC cases and randomly sampled controls with minor benign skin conditions diagnosed between July 2006 and September 2010 were identified through Yale University's Dermatopathology database. Participants completed a structured in-person interview, self-administered questionnaires, and provided a saliva sample. We gathered self-reported eye color, skin color (inner upper arm), hair color (natural color), freckling on the arms (based on images), number of moles on the back ≥ 5 mm (clear acetate size template), mole removal, skin reaction to sunlight for the first time in the summer for one hour without sunscreen, skin reaction after repeated and prolonged exposure to sunlight, family history of melanoma and NMSC, and indoor and outdoor ultraviolet (UV) radiation exposure.
We assessed the predictive performance of our novel risk prediction model and two models in the literature via summary measures of calibration, misclassification, and discrimination. We employed bootstrapping to better reflect the area under the receiver operating characteristic curve (AUC) expected when the model is tested on an independent, but similar set of patients. To investigate if indoor tanning and MC1R improved prediction performance over our early-onset BCC base model, we evaluated the regression coefficients for the markers in the expanded risk model and the corresponding likelihood ratio test statistic. All statistical tests were two-sided and analyses were performed in the statistical software R (Version 3.0.2).
Results: An existing model by Han et al. (2006) included seven MC1R variants and in our data the bootstrapped AUC for this model was 0.72 (95% CI, 0.66-0.78). Another existing model by Smith et al. (2012) with MC1R and indoor tanning resulted in a bootstrapped AUC of 0.69 (95% CI 0.63-0.75) in our population. Our base model, which included hair color, skin color, skin reaction with prolonged sun exposure, education, freckles on arm, family history of NMSC, and outdoor sun exposure in warm months, had greater predictive ability (bootstrapped AUC=0.75, 95% CI=0.72-0.79) than the existing models we evaluated. We also found that our model was significantly improved when we added ever indoor tanning, burns from indoor tanning, and the R151C MC1R variant (bootstrapped AUC=0.77, 95% CI, 0.74-0.81).
Conclusions: Our risk prediction model incorporating both MC1R and indoor tanning in the risk of early-onset BCC, validates and extends the work of other skin cancer risk prediction models and emphasizes the value of considering both genotype and indoor tanning in skin cancer risk prediction in young people. Therefore, in addition to the typical skin cancer characteristics clinicians rely on, assessing and counseling young people to reduce both indoor and outdoor UV exposure is needed to reduce BCC risk.
Citation Format: Annette M. Molinaro, Leah M. Ferrucci, Brenda Cartmel, Erikka Loftfield, David J. Leffell, Allen E. Bale, Susan T. Mayne. Impact of indoor tanning and MC1R genotype on basal cell carcinoma risk in young people. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A50.
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