title: Does the addition of information on genotype improve prediction of the risk of melanoma and nonmelanoma skin cancer beyond that obtained from skin phenotype?
abstract: The authors quantified improvement in predicting cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin made possible by information on common variants of the melanocortin-1 receptor gene (MC1R) in a 1998-1999 population-based case-control study of subjects aged 20-59 years of northern European ancestry in Tasmania, Australia. Melanin density at the upper inner arm was estimated by spectrophotometry. DNA samples were genotyped for five MC1R variants: Val60Leu, Asp84Glu, Arg151Cys, Arg160Trp, and Asp294His. Among controls (n = 267), variant carriers, versus noncarriers, had lower (p < 0.01) mean melanin concentrations. Increased risk conferred by genotype was restricted mainly to those with the darkest skins: for subjects with at least 2% melanin, the odds of carrying each additional variant were higher for cutaneous malignant melanoma (n = 39; odds ratio = 1.45, 95% confidence interval: 0.87, 2.44), basal cell carcinoma (n = 35; odds ratio = 1.86, 95% confidence interval: 1.14, 3.02), and squamous cell carcinoma (n = 42; odds ratio = 2.67, 95% confidence interval: 1.50, 4.74) cases than for controls (n = 135). Adding MC1R information to prediction based on age, sex, and cutaneous melanin increased the area under the receiver operating characteristic curve by 1.4% (cutaneous malignant melanoma), 3.2% (basal cell carcinoma), or 2.0% (squamous cell carcinoma). The improvement in prediction was probably too small to be valuable in a clinical setting.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: James M
authors.initials: JM
authors.lastname: Stankovich
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Dickinson
authors.forename: Anne
authors.initials: A
authors.lastname: Reilly
authors.forename: Jan
authors.initials: J
authors.lastname: Williamson
authors.forename: Rosie
authors.initials: R
authors.lastname: Ashbolt
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D000328:Adult; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008543:Melanins / Q000032:analysis; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011237:Predictive Value of Tests; D012372:ROC Curve; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012042:Registries; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013053:Spectrophotometry / Q000379:methods / Q000592:standards; D013648:Tasmania / Q000453:epidemiology
chemical_list: D008543:Melanins; D044102:Receptor, Melanocortin, Type 1