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.
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Authors | Terence Dwyer, James M Stankovich, Leigh Blizzard, Liesel M FitzGerald, Joanne L Dickinson, Anne Reilly, Jan Williamson, Rosie Ashbolt, Marianne Berwick, Michèle M Sale |
Journal | American journal of epidemiology
(Am J Epidemiol)
Vol. 159
Issue 9
Pg. 826-33
(May 01 2004)
ISSN: 0002-9262 [Print] United States |
PMID | 15105175
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
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Chemical References |
- Melanins
- Receptor, Melanocortin, Type 1
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Topics |
- Adult
- Carcinoma, Basal Cell
(epidemiology, genetics)
- Carcinoma, Squamous Cell
(epidemiology, genetics)
- Case-Control Studies
- Female
- Gene Frequency
- Genetic Predisposition to Disease
(epidemiology, genetics)
- Genetic Testing
(methods, standards)
- Genetic Variation
(genetics)
- Genotype
- Humans
- Male
- Melanins
(analysis)
- Melanoma
(epidemiology, genetics)
- Middle Aged
- Population Surveillance
(methods)
- Predictive Value of Tests
- ROC Curve
- Receptor, Melanocortin, Type 1
(genetics)
- Registries
- Risk Assessment
(methods)
- Risk Factors
- Skin
(chemistry)
- Skin Neoplasms
(epidemiology, genetics)
- Spectrophotometry
(methods, standards)
- Tasmania
(epidemiology)
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