There is strong evidence that a combination of genotypes, endogenous physiology, and exogenous exposures influence melanoma risk. However, the interaction of these factors in melanoma etiology remains unclear. In particular, inherited genotypes involved in response to environmental exposures (e.g., UV sun exposure) may modify an individual's risk of developing melanoma. Knowledge about interactions of these factors in melanoma etiology 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 and other risk factors. This study will address a number of specific hypotheses. First, we will evaluate whether candidate susceptibility genotypes are associated with melanoma in a case-control analysis. Second, we will evaluate whether genotypes and other risk factors interact in melanoma etiology, and whether knowledge of genotypes will improve our understanding of melanoma etiology once other risk factors (e.g., dysplastic nevi, UV sun exposure, hair/eye color) are known. Third, we will evaluate whether genotypes and other exposures distinguish individuals with dysplastic nevi who do and do not eventually develop invasive melanoma. 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 400 melanoma cases with dysplastic nevi, 400 melanoma cases without dysplastic nevi, 400 subjects with dysplastic nevi but no history of melanoma, and 400 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.
| 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 |
| Gimotty, Phyllis A; Van Belle, Patricia; Elder, David E et al. (2005) Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma. J Clin Oncol 23:8048-56 |
| Gimotty, Phyllis A; Guerry, DuPont; Ming, Michael E et al. (2004) Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging. J Clin Oncol 22:3668-76 |
| 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 |
| Zeigler-Johnson, Charnita; Panossian, Saarene; Gueye, Serigne M et al. (2004) Population differences in the frequency of the agouti signaling protein g.8818a>G polymorphism. Pigment Cell Res 17:185-7 |
| Seykora, John T; Jih, Debbie; Elenitsas, Rosalie et al. (2003) Gene expression profiling of melanocytic lesions. Am J Dermatopathol 25:6-11 |
| Kanetsky, Peter A; Swoyer, Jennifer; Panossian, Saarene et al. (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70:770-5 |
| Blackwood, M Anne; Holmes, Robin; Synnestvedt, Marie et al. (2002) Multiple primary melanoma revisited. Cancer 94:2248-55 |
| McGinnis, Karen S; Lessin, Stuart R; Elder, David E et al. (2002) Pathology review of cases presenting to a multidisciplinary pigmented lesion clinic. Arch Dermatol 138:617-21 |
| Rebbeck, Timothy R; Kanetsky, Peter A; Walker, Amy H et al. (2002) P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev 11:782-4 |
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