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 |
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.
Publications
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, 2020-08-11; , .
EPub date: 2020-08-11.
PMID: 32780924
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
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
Related Citations
Tumor progression, early diagnosis and prognosis of melanoma.
Authors: Elder D.
.
Source: Acta oncologica (Stockholm, Sweden), 1999; 38(5), p. 535-47.
PMID: 10427941
Related Citations
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
Related Citations