Grant Number:	5R01CA092428-05 Interpret this number
Primary Investigator:	Kanetsky, Peter
Organization:	University Of Pennsylvania
Project Title:	Molecular Epidemiology of Melanoma
Fiscal Year:	2006

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.




MC1R variants in relation to naevi in melanoma cases and controls: a pooled analysis from the M-SKIP project.
Authors: Stefanaki I. , Stratigos A.J. , Kypreou K.P. , Evangelou E. , Gandini S. , Maisonneuve P. , Polsky D. , Lazovich D. , Newton-Bishop J. , Kanetsky P.A. , et al. .
Source: Journal of the European Academy of Dermatology and Venereology : JEADV, 2021 Feb; 35(2), p. e135-e138.
EPub date: 2020-09-06.
PMID: 32780924
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MC1R variants and cutaneous melanoma risk according to histological type, body site, and Breslow thickness: a pooled analysis from the M-SKIP project.
Authors: Caini S. , Gandini S. , Botta F. , Tagliabue E. , Raimondi S. , Nagore E. , Zanna I. , Maisonneuve P. , Newton-Bishop J. , Polsky D. , et al. .
Source: Melanoma research, 2020 Oct; 30(5), p. 500-510.
PMID: 32898390
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MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.
Authors: Pellegrini C. , Botta F. , Massi D. , Martorelli C. , Facchetti F. , Gandini S. , Maisonneuve P. , Avril M.F. , Demenais F. , Bressac-de Paillerets B. , et al. .
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EPub date: 2019-03-12.
PMID: 30872112
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Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma.
Authors: Taylor N.J. , Thomas N.E. , Anton-Culver H. , Armstrong B.K. , Begg C.B. , Busam K.J. , Cust A.E. , Dwyer T. , From L. , Gallagher R.P. , et al. .
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PMID: 27101944
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Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project.
Authors: Tagliabue E. , Gandini S. , García-Borrón J.C. , Maisonneuve P. , Newton-Bishop J. , Polsky D. , Lazovich D. , Kumar R. , Ghiorzo P. , Ferrucci L. , et al. .
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EPub date: 2016-05-29.
PMID: 27251790
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Development and validation of a melanoma risk score based on pooled data from 16 case-control studies.
Authors: Davies J.R. , Chang Y.M. , Bishop D.T. , Armstrong B.K. , Bataille V. , Bergman W. , Berwick M. , Bracci P.M. , Elwood J.M. , Ernstoff M.S. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015 May; 24(5), p. 817-24.
EPub date: 2015-02-24.
PMID: 25713022
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Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study.
Authors: Davies J.R. , Randerson-Moor J. , Kukalizch K. , Harland M. , Kumar R. , Madhusudan S. , Nagore E. , Hansson J. , Höiom V. , Ghiorzo P. , et al. .
Source: Pigment cell & melanoma research, 2012 May; 25(3), p. 384-94.
EPub date: 2012-03-16.
PMID: 22325793
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Does MC1R genotype convey information about melanoma risk beyond risk phenotypes?
Authors: Kanetsky P.A. , Panossian S. , Elder D.E. , Guerry D. , Ming M.E. , Schuchter L. , Rebbeck T.R. .
Source: Cancer, 2010-05-15; 116(10), p. 2416-28.
PMID: 20301115
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Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls.
Authors: Chang Y.M. , Barrett J.H. , Bishop D.T. , Armstrong B.K. , Bataille V. , Bergman W. , Berwick M. , Bracci P.M. , Elwood J.M. , Ernstoff M.S. , et al. .
Source: International journal of epidemiology, 2009 Jun; 38(3), p. 814-30.
EPub date: 2009-04-08.
PMID: 19359257
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Assessment of polymorphic variants in the melanocortin-1 receptor gene with cutaneous pigmentation using an evolutionary approach.
Authors: Kanetsky P.A. , Ge F. , Najarian D. , Swoyer J. , Panossian S. , Schuchter L. , Holmes R. , Guerry D. , Rebbeck T.R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2004 May; 13(5), p. 808-19.
PMID: 15159314
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