Host Phenotype Characteristics and MC1R in Relation to Early-Onset Basal Cell Carcinoma

• Published in: Journal of investigative dermatology Vol. 132; no. 4; pp. 1272 - 1279
• Main Authors: Ferrucci, Leah M., Cartmel, Brenda, Molinaro, Annette M., Gordon, Patricia B., Leffell, David J., Bale, Allen E., Mayne, Susan T.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2012; Nature Publishing Group; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Biopsy; Carcinoma, Basal Cell - epidemiology; Carcinoma, Basal Cell - genetics; Case-Control Studies; Dermatology; Female; Genetic Variation - genetics; Genotype; Hair Color; Humans; Male; Medical sciences; Phenotype; Receptor, Melanocortin, Type 1 - genetics; Retrospective Studies; Risk Factors; Skin - pathology; Skin - radiation effects; Skin Neoplasms - epidemiology; Skin Neoplasms - genetics; Skin Pigmentation; Time Factors; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet Rays - adverse effects; Skin disease; Phenotype; Basal cell carcinoma; Characteristics; Dermatology; Malignant tumor; Cancer
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2011.402

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under the age of 40 years. 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 the age of 40 years were identified through Yale's Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for 1 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 case status (37% of cases) than a single BCC case status. MC1R, number of moles, skin reaction to first summer sun for 1 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.