title: Development of a melanoma risk prediction model incorporating MC1R genotype and indoor tanning exposure: impact of mole phenotype on model performance.
abstract: BACKGROUND
  Identifying individuals at increased risk for melanoma could potentially improve public health through targeted surveillance and early detection. Studies have separately demonstrated significant associations between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. Existing melanoma risk prediction models do not include these factors; therefore, we investigated their potential to improve the performance of a risk model.
  
  
  METHODS
  Using 875 melanoma cases and 765 controls from the population-based Minnesota Skin Health Study we compared the predictive ability of a clinical melanoma risk model (Model A) to an enhanced model (Model F) using receiver operating characteristic (ROC) curves. Model A used self-reported conventional risk factors including mole phenotype categorized as "none", "few", "some" or "many" moles. Model F added MC1R genotype and measures of indoor and outdoor UV exposure to Model A. We also assessed the predictive ability of these models in subgroups stratified by mole phenotype (e.g. nevus-resistant ("none" and "few" moles) and nevus-prone ("some" and "many" moles)).
  
  
  RESULTS
  Model A (the reference model) yielded an area under the ROC curve (AUC) of 0.72 (95% CI = 0.69, 0.74). Model F was improved with an AUC = 0.74 (95% CI = 0.71-0.76, p<0.01). We also observed substantial variations in the AUCs of Models A & F when examined in the nevus-prone and nevus-resistant subgroups.
  
  
  CONCLUSIONS
  These results demonstrate that adding genotypic information and environmental exposure data can increase the predictive ability of a clinical melanoma risk model, especially among nevus-prone individuals.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Penn
authors.affiliation: Department of Population Health and Environmental Medicine, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: Meng
authors.initials: M
authors.lastname: Qian
authors.affiliation: Department of Population Health and Environmental Medicine, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: Enhan
authors.initials: E
authors.lastname: Zhang
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: Elise
authors.initials: E
authors.lastname: Ng
authors.affiliation: Department of Population Health and Environmental Medicine, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico Cancer Center, Albuquerque, New Mexico, United States of America.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: DeAnn
authors.initials: D
authors.lastname: Lazovich
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York City, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Polsky
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019540:Area Under Curve; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D015233:Models, Statistical; D010641:Phenotype; D062486:Public Health Surveillance; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D015203:Reproducibility of Results; D012306:Risk; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D055108:Sunbathing; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D044102:Receptor, Melanocortin, Type 1