Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under age 40. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under age 40 were identified through Yale’s Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for one hour [severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08–36.94] and skin color (very fair vs. olive OR=11.06, 95% CI=5.90–20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37–5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC cases status (37% of cases) than single BCC case status. MC1R, number of moles, skin reaction to first summer sun for one hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low-risk of skin cancer.