Journal Article

Does the Addition of Information on Genotype Improve Prediction of the Risk of Melanoma and Nonmelanoma Skin Cancer beyond That Obtained from Skin Phenotype?

Terence Dwyer, James M. Stankovich, Leigh Blizzard, Liesel M. FitzGerald, Joanne L. Dickinson, Anne Reilly, Jan Williamson, Rosie Ashbolt, Marianne Berwick and Michèle M. Sale

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 159, issue 9, pages 826-833
Published in print May 2004 | ISSN: 0002-9262
Published online May 2004 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwh120
Does the Addition of Information on Genotype Improve Prediction of the Risk of Melanoma and Nonmelanoma Skin Cancer beyond That Obtained from Skin Phenotype?

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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.

Keywords: case-control studies; epidemiologic factors; genetics; melanins; polymorphism (genetics); receptor, melanocortin, type 1; Abbreviations: CMM, cutaneous malignant melanoma; MC1R, melanocortin-1 receptor gene; PCR, polymerase chain reaction; ROC, receiver operating characteristic.

Journal Article.  5492 words.  Illustrated.

Subjects: Public Health and Epidemiology

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