OCA2 and MC1R interact with UV exposure to determine nevus counts and freckle scores in children

Abstract

Melanoma is an important public health problem, where efforts at prevention are key. Risk of melanoma is determined largely by the interaction of childhood and adolescent UV exposure with melanoma risk genes. A deeper understanding of how risk genes interact with childhood UV exposure to determine phenotypic risk indicators such as nevus counts and freckle scores has important public health implications. The Melanocortin 1 Receptor (MC1R) is a key melanoma risk gene that when mutated causes the red hair color phenotype, including poor tanning and susceptibility to sunburns and melanoma. MC1R interacts with the Oculocutaneous Albinism Type II (OCA2) gene to determine pigmentation phenotypes. We utilized the Colorado Kids Sun Care Program (CKSP) to study how MC1R and OCA2 interact with different UV exposure profiles to influence sun-sensitivity phenotypes. The CKSP includes a cohort of over 900 children who have been followed from ages 6 to 10 with annual skin exams and data collection on nevus counts, sun exposure, phenotype and behavioral variables. The genotyping of MC1R and OCA2 and correlation studies with phenotypic measures show association between the major blue/brown eye color OCA2/HERC2 rs12913832 SNP, UV exposure and nevus counts. The data suggest that individuals who are homozygous for this SNP are particularly sensitive to modification of nevus counts by UV exposure. Furthermore, this modification is preferred in individuals with intermittent vs. chronic UV exposure behaviors. We have similarly examined the interactions of these variables with MC1R variants to illustrate how different genes interact with different UV exposure profiles to give maximal nevus counts in children. The data generated by this study highlights the importance of preventive and personalized medicine and will be crucial for the selection of individuals with nevus and melanoma susceptibility genotypes who may be targeted for primary prevention