Pigmentation phenotypes (e.g., hair color) and response to sun exposure (e.g., freckling, sunburns) have been associated with melanoma risk. However, there is also strong evidence that a combination of genotypes, endogenous physiology, and exogenous exposures influence melanoma risk. In particular, inherited genotypes involved in pigmentation pathways and response to environmental exposures (e.g., UV sun exposure) may modify an individual's risk of developing melanoma. These genes include those involved in melanogenesis, such as the melanocortin 1 receptor (MC1R), tyrosinase (TYR), the tyrosine-related proteins (TRP1, TRP2), and the P gene. Knowledge about interactions of these genes in addition to pigmentation characteristics and UV sun exposure may improve the ability to identify individuals at increased melanoma risk. This knowledge may in turn be used to target individuals for primary or secondary melanoma prevention strategies. We propose a case-control study that will directly address the complex, multifactorial etiology of melanoma that involves the interaction of genotypes involved in pigmentation pathways and other risk factors. This study will address a number of specific hypotheses. First, we will characterize candidate susceptibility genotypes. Second, we will evaluate whether genotypes are associated with pigmentation characteristics (in particular those that are associated with melanoma risk), and whether genotypes are associated with tumor characteristics, including stage, grade, and age at diagnosis., Finally, we will evaluate whether these genotypes are involved in melanoma etiology, and whether these genotypes interact with one another and other melanoma risk factors. In order to address these hypotheses, we will undertake a study using the extensive resources of the Pigmented Lesion Group at the University of Pennsylvania. The sample will consist of 1000 melanoma cases and 1000 controls. Risk factor information will be obtained by questionnaire, a DNA biosample will be collected using a non-invasive cheek swab method, and diagnostic pathology information will be collected using a systematic approach. Analyses will be undertaken to evaluate the role of candidate genotypes and other risk factors in melanoma etiology, including genotype by environment interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA092428-05
Application #
7088950
Study Section
Special Emphasis Panel (ZRG1-SNEM-5 (02))
Program Officer
Seminara, Daniela
Project Start
2002-07-29
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$401,292
Indirect Cost
Name
University of Pennsylvania
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Tagliabue, Elena; Gandini, Sara; García-Borrón, José C et al. (2016) Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project. J Invest Dermatol 136:1914-1917
Taylor, Nicholas J; Thomas, Nancy E; Anton-Culver, Hoda et al. (2016) Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma. Int J Cancer 139:1217-22
Davies, John R; Chang, Yu-mei; Bishop, D Timothy et al. (2015) Development and validation of a melanoma risk score based on pooled data from 16 case-control studies. Cancer Epidemiol Biomarkers Prev 24:817-24
Davies, John R; Randerson-Moor, Juliette; Kukalizch, Kairen et al. (2012) Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res 25:384-94
Kanetsky, Peter A; Panossian, Saarene; Elder, David E et al. (2010) Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? Cancer 116:2416-28
Chang, Yu-mei; Barrett, Jennifer H; Bishop, D Timothy et al. (2009) Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls. Int J Epidemiol 38:814-30
Kanetsky, Peter A; Ge, Fan; Najarian, Derek et al. (2004) Assessment of polymorphic variants in the melanocortin-1 receptor gene with cutaneous pigmentation using an evolutionary approach. Cancer Epidemiol Biomarkers Prev 13:808-19