Does the addition of information on genotype improve prediction of the risk of melanoma and nonmelanoma skin cancer beyond that obtained from skin phenotype? Journal Article
| Authors: | Dwyer, T.; Stankovich, J. M.; Blizzard, L.; FitzGerald, L. M.; Dickinson, J. L.; Reilly, A.; Williamson, J.; Ashbolt, R.; Berwick, M.; Sale, M. M. |
| Article 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. |
| Keywords: | adult; controlled study; middle aged; major clinical study; case control study; genetics; case-control studies; squamous cell carcinoma; carcinoma, squamous cell; cancer risk; methodology; accuracy; genetic predisposition to disease; melanoma; melanin; basal cell carcinoma; skin neoplasms; skin cancer; genetic variability; genotype; gene frequency; risk factors; health survey; validation study; prediction; risk factor; age; risk assessment; confidence interval; skin; standard; skin tumor; population research; chemistry; register; registries; quantitative analysis; prediction and forecasting; predictive value of tests; australia; gender; density; leucine; genetic predisposition; genetic screening; glutamic acid; population surveillance; melanocortin 1 receptor; receptor, melanocortin, type 1; carcinoma, basal cell; dna determination; aspartic acid; cysteine; roc curve; histidine; valine; genetic polymorphism; receiver operating characteristic; tryptophan; genotype phenotype correlation; skin color; melanins; arginase; variation (genetics); spectrophotometry; cancer; humans; human; male; female; article; epidemiologic factors; polymorphism (genetics); tasmania |
| Journal Title: | American Journal of Epidemiology |
| Volume: | 159 |
| Issue: | 9 |
| ISSN: | 0002-9262 |
| Publisher: | Oxford University Press |
| Date Published: | 2004-05-01 |
| Start Page: | 826 |
| End Page: | 833 |
| Language: | English |
| DOI: | 10.1093/aje/kwh120 |
| PROVIDER: | scopus |
| PUBMED: | 15105175 |
| DOI/URL: | |
| Notes: | Am. J. Epidemiol. -- Cited By (since 1996):34 -- Export Date: 16 June 2014 -- CODEN: AJEPA -- Source: Scopus |
