) One of my academic career goals is to develop molecular and genetic epidemiologic research to identify etiologic factors associated with pigmented lesions, including cutaneous malignant melanoma and multiple primary melanoma (MPM). Determination of susceptibility genes for melanoma can facilitate identification of those at increased risk for disease and may result in increase public and individual efforts of prevention and early detection. The potential impact of these measures is great, as melanoma incidence has reached epidemic proportions and mortality due to melanoma has slowly increased over the past decades. The Preventive Oncology Academic Award will give me an opportunity to become a competent melanoma molecular epidemiologist. To this end, I will advance my academic understanding of melanoma through further education in the basic sciences, molecular biology/epidemiology, genetics, and clinical decision making. Practical experience will be gained through participation in molecular laboratory biology, with a focus on methodologies used in molecular epidemiology. Two research projects are proposed to explore the association of a candidate susceptibility gene and development of melanoma. Mutations in the candidate gene of interest, the melanocortin-1 receptor (MC1R), may affect melanin synthesis, resulting in an increased potential for cellular DNA damage that may lead to melanocytic carcinogenesis. The goals of the first study are i) to determine the number and types of gene variants among persons with MPM and single cutaneous melanoma (SCM), and ii) to test whether these mutations play a role in the subsequent development of MPM. The results will contribute greatly to the epidemiologic literature on candidate susceptibility genes associated with melanoma and will help focus primary and secondary prevention for persons at increased risk for secondary, primary melanomas. The second project evaluates whether allelic variants in the MC1R gene explain the pattern of melanoma in families prone to melanoma. Result from this project may provide valuable insight into the genetic predisposition to melanoma seen in some families, and may lead to more efficient mechanisms of primary prevention and clinical follow-up within these families.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA080700-04
Application #
6653230
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2000-09-06
Project End
2005-08-31
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
4
Fiscal Year
2003
Total Cost
$130,128
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
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
Kricker, Anne; Armstrong, Bruce K; Goumas, Chris et al. (2010) MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study. Cancer Causes Control 21:2137-47
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
Goldstein, Alisa M; Chan, May; Harland, Mark et al. (2007) Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet 44:99-106
Landi, Maria Teresa; Bauer, Jurgen; Pfeiffer, Ruth M et al. (2006) MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313:521-2
Kanetsky, Peter A; Rebbeck, Timothy R; Hummer, Amanda J et al. (2006) Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res 66:9330-7
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