title: Interactions between ultraviolet light and MC1R and OCA2 variants are determinants of childhood nevus and freckle phenotypes.
abstract: BACKGROUND
  Melanocytic nevi (moles) and freckles are well known biomarkers of melanoma risk, and they are influenced by similar UV light exposures and genetic susceptibilities to those that increase melanoma risk. Nevertheless, the selective interactions between UV exposures and nevus and freckling genes remain largely undescribed.
  
  
  METHODS
  We conducted a longitudinal study from ages 6 through 10 years in 477 Colorado children who had annual information collected for sun exposure, sun protection behaviors, and full body skin exams. MC1R and HERC2/OCA2 rs12913832 were genotyped and linear mixed models were used to identify main and interaction effects.
  
  
  RESULTS
  All measures of sun exposure (chronic, sunburns, and waterside vacations) contributed to total nevus counts, and cumulative chronic exposure acted as the major driver of nevus development. Waterside vacations strongly increased total nevus counts in children with rs12913832 blue eye color alleles and facial freckling scores in those with MC1R red hair color variants. Sunburns increased the numbers of larger nevi (≥2 mm) in subjects with certain MC1R and rs12913832 genotypes.
  
  
  CONCLUSIONS
  Complex interactions between different UV exposure profiles and genotype combinations determine nevus numbers and size, and the degree of facial freckling.
  
  
  CONCLUSIONS
  Our findings emphasize the importance of implementing sun-protective behavior in childhood regardless of genetic make-up, although children with particular genetic variants may benefit from specifically targeted preventive measures to counteract their inherent risk of melanoma. Moreover, we demonstrate, for the first time, that longitudinal studies are a highly powered tool to uncover new gene-environment interactions that increase cancer risk.
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Barón
authors.affiliation: Department of Community and Behavioral Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Asdigian
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gonzalez
authors.affiliation: Department of Community and Behavioral Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Jenny
authors.initials: J
authors.lastname: Aalborg
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Tamara
authors.initials: T
authors.lastname: Terzian
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Regan A
authors.initials: RA
authors.lastname: Stiegmann
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Enrique C
authors.initials: EC
authors.lastname: Torchia
authors.affiliation: Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Dermatology Service, Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado. Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Dellavalle
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Morelli
authors.affiliation: Kaiser Permanente Health Plan of Colorado, Denver, Colorado.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Mokrohisky
authors.affiliation: Department of Community and Behavioral Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Crane
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. neil.box@ucdenver.edu.
authors.forename: Neil F
authors.initials: NF
authors.lastname: Box
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008548:Melanosis / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics*; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D014466:Ultraviolet Rays
chemical_list: D044102:Receptor, Melanocortin, Type 1