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Grant Details

Grant Number: 5P01CA075434-04 Interpret this number
Primary Investigator: Guerry, Dupont
Organization: University Of Pennsylvania
Project Title: Prediction and Modification of Melanoma Risk
Fiscal Year: 2000
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Abstract

Melanoma is a potentially lethal skin cancer. Its incidence and mortality rates are increasing faster than those of most other malignancies. The over-arching theme of this Program is melanocytic tumor progression, the process that epidemiologically, mechanistically, and clinically links environmental exposure, the precursor state, primary melanoma with and without invasive and metastatic potential, and metastasis. Our goal is to decrease mortality from melanoma, a malignancy for which there are compelling arguments for interventions directed to high risk cohorts and patients with primary disease. To achieve this, three projects will be focused on aspects of early tumor progression to: 1) define the mechanisms of and predict heightened melanoma susceptibility, 2) ameliorate this risk by rational chemoprevention, and 3) quantify the risk of metastasis in patients with primary disease to allow selection of patients for new staging procedures and adjuvant therapies. Project 1 is a case-control study that addresses the multifactorial etiology of melanoma. It asks whether candidate genotypes (ascertained from DNA self-collected using a non-invasive method) and other risk factors interact in and help explain melanoma etiology and whether these distinguish persons developing melanoma in a high risk cohort. This cohort is made up of individual s with nevi (dysplastic nevi) that are melanoma risk markers and potential precursors. Project 2 utilizes a randomized trial of topical tretinoin and 4-HPR (fenretinide) to test chemoprevention in another cohort with dysplastic nevi. It uses clinical and histologic changes in these intermediate markers of tumor progression as the endpoints and will correlate the in situ expression and distribution of retinoid receptors with response and with markers of apoptosis and of tumor infiltrating lymphocyte (TIL) activity. Project 3 employs clinical and pathological data from a cohort of patients followed for 10 years as variables in the construction and validation of credible, accurate, and generalizable prognostic models. These are a prediction rule to identify non-metastasizing lesions and a probability model to estimate individual risks of metastasis in patients with more advanced primaries. Variables include marker of melanoma cell proliferation and cytolytic TIL. These variables will also be studied in a prospective series to test as an independent variable an RT-PCR based assay for circulating melanoma cells (expression in blood of the gene for the pigment-related protein tyrosinase). To maximize productivity and efficiency the projects are served by three cores: a coordinating administrative Core, a Data Management and Analysis core, and a Pigmented Lesion Clinical/Pathology Core (PLCC). For more than 20 years the PLCC has ascertained and tracked over 4000 melanoma patients.

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Publications

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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Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma.
Authors: Gimotty P.A. , Van Belle P. , Elder D.E. , Murry T. , Montone K.T. , Xu X. , Hotz S. , Raines S. , Ming M.E. , Wahl P. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2005-11-01; 23(31), p. 8048-56.
PMID: 16258103
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Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging.
Authors: Gimotty P.A. , Guerry D. , Ming M.E. , Elenitsas R. , Xu X. , Czerniecki B. , Spitz F. , Schuchter L. , Elder D. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2004-09-15; 22(18), p. 3668-76.
EPub date: 2004-08-09.
PMID: 15302909
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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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Population differences in the frequency of the agouti signaling protein g.8818a>G polymorphism.
Authors: Zeigler-Johnson C. , Panossian S. , Gueye S.M. , Jalloh M. , Ofori-Adjei D. , Kanetsky P.A. .
Source: Pigment cell research, 2004 Apr; 17(2), p. 185-7.
PMID: 15016309
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Gene expression profiling of melanocytic lesions.
Authors: Seykora J.T. , Jih D. , Elenitsas R. , Horng W.H. , Elder D.E. .
Source: The American Journal of dermatopathology, 2003 Feb; 25(1), p. 6-11.
PMID: 12544092
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P gene as an inherited biomarker of human eye color.
Authors: Rebbeck T.R. , Kanetsky P.A. , Walker A.H. , Holmes R. , Halpern A.C. , Schuchter L.M. , Elder D.E. , Guerry D. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002 Aug; 11(8), p. 782-4.
PMID: 12163334
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Pathology review of cases presenting to a multidisciplinary pigmented lesion clinic.
Authors: McGinnis K.S. , Lessin S.R. , Elder D.E. , Guerry D. , Schuchter L. , Ming M. , Elenitsas R. .
Source: Archives of dermatology, 2002 May; 138(5), p. 617-21.
PMID: 12020222
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Multiple primary melanoma revisited.
Authors: Blackwood M.A. , Holmes R. , Synnestvedt M. , Young M. , George C. , Yang H. , Elder D.E. , Schuchter L.M. , Guerry D. , Ganguly A. .
Source: Cancer, 2002-04-15; 94(8), p. 2248-55.
PMID: 12001124
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A polymorphism in the agouti signaling protein gene is associated with human pigmentation.
Authors: Kanetsky P.A. , Swoyer J. , Panossian S. , Holmes R. , Guerry D. , Rebbeck T.R. .
Source: American journal of human genetics, 2002 Mar; 70(3), p. 770-5.
EPub date: 2002-02-06.
PMID: 11833005
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Interaction of glutathione S-transferase M1 and T1 genotypes and malignant melanoma.
Authors: Kanetsky P.A. , Holmes R. , Walker A. , Najarian D. , Swoyer J. , Guerry D. , Halpern A. , 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, 2001 May; 10(5), p. 509-13.
PMID: 11352862
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TIA-1 positive tumor-infiltrating lymphocytes in nevi and melanomas.
Authors: Lyle S. , Salhany K.E. , Elder D.E. .
Source: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2000 Jan; 13(1), p. 52-5.
PMID: 10658910
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Collection of genomic DNA by buccal swabs for polymerase chain reaction-based biomarker assays.
Authors: Walker A.H. , Najarian D. , White D.L. , Jaffe J.F. , Kanetsky P.A. , Rebbeck T.R. .
Source: Environmental health perspectives, 1999 Jul; 107(7), p. 517-20.
PMID: 10378997
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Progression-related expression of beta3 integrin in melanomas and nevi.
Authors: Van Belle P.A. , Elenitsas R. , Satyamoorthy K. , Wolfe J.T. , Guerry D. , Schuchter L. , Van Belle T.J. , Albelda S. , Tahin P. , Herlyn M. , et al. .
Source: Human pathology, 1999 May; 30(5), p. 562-7.
PMID: 10333228
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Tumor progression, early diagnosis and prognosis of melanoma.
Authors: Elder D. .
Source: Acta oncologica (Stockholm, Sweden), 1999; 38(5), p. 535-47.
PMID: 10427941
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Validation of a melanoma prognostic model.
Authors: Margolis D.J. , Halpern A.C. , Rebbeck T. , Schuchter L. , Barnhill R.L. , Fine J. , Berwick M. .
Source: Archives of dermatology, 1998 Dec; 134(12), p. 1597-601.
PMID: 9875200
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