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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA066032-09 Interpret this number
Primary Investigator: Titus-Ernstoff, Linda
Organization: Dartmouth College
Project Title: Melanoma Pathogenesis
Fiscal Year: 2006
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DESCRIPTION (provided by applicant): We propose a study of melanoma pathogenesis involving two parallel and mutually informative primary aims. First, we will follow melanoma cases (who were previously enrolled in our case-control study) for a second primary melanoma. Virtually all previous studies of multiple primary melanoma were based on clinical or registry databases, which lack follow-up of the cohort at risk. Thus, the rates and risks of this disease remain essentially unknown. Second, we will characterize chromosome 9p21 alterations in a progressive spectrum of melanocytic lesions pertinent to melanoma pathogenesis (benign nevi, atypical nevi, and melanoma). Chromosome 9p21 contains the tumor suppressor gene p16, and our pilot studies indicate that alterations of this region precede the development of morphologic atypia. We will investigate 9p21 alterations (chromosome 9p21 LOH, p16 deletion, and p16 methylation) using lesions already obtained through the parent study, and new lesions obtained through the proposed follow-up effort. We hypothesize that chromosome 9p21 alterations characterize a variant melanoma pathogenesis involving atypical nevi, superficial spreading melanoma, and high risk for multiple primary melanomas. Thus, we will examine chromosome 9p21 alterations in relation to atypical nevi, melanoma histologic subtype, and risk of multiple primary melanoma. We will also examine atypical nevi and superficial spreading melanoma in relation to risk of multiple primary melanoma. Finally, we will explore traditional epidemiologic risk factors in relation to chromosome 9p21 alterations and in relation to risk of multiple primary melanoma. This innovative and costeffective proposal benefits substantially from the work accomplished in our recently completed case-control study, including the prior collection of interview data, the dermatologist-conducted skin examination, the pathology review of all melanocytic lesions, the retrieval and sampling (i.e., slide preparation) of pathology specimens, and the refinement of laboratory techniques for analyzing chromosome 9p21 alterations.

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Pigmentary Characteristics And Moles In Relation To Melanoma Risk
Authors: Titus-Ernstoff L. , Perry A.E. , Spencer S.K. , Gibson J.J. , Cole B.F. , Ernstoff M.S. .
Source: International Journal Of Cancer, 2005-08-10 00:00:00.0; 116(1), p. 144-9.
PMID: 15761869
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Multiple Primary Melanoma: Two-year Results From A Population-based Study
Authors: Titus-Ernstoff L. , Perry A.E. , Spencer S.K. , Gibson J. , Ding J. , Cole B. , Ernstoff M.S. .
Source: Archives Of Dermatology, 2006 Apr; 142(4), p. 433-8.
PMID: 16618861
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Factors Associated With Atypical Moles In New Hampshire, Usa
Authors: Titus-Ernstoff L. , Ding J. , Perry A.E. , Spencer S.K. , Cole B.F. , Ernstoff M.S. .
Source: Acta Dermato-venereologica, 2007; 87(1), p. 43-8.
PMID: 17225015
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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.
PMID: 19359257
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Recent Skin Self-examination And Doctor Visits In Relation To Melanoma Risk And Tumour Depth
Authors: Titus L.J. , Clough-Gorr K. , Mackenzie T.A. , Perry A. , Spencer S.K. , Weiss J. , Abrahams-Gessel S. , Ernstoff M.S. .
Source: The British Journal Of Dermatology, 2013 Mar; 168(3), p. 571-6.
PMID: 22897437
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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.
PMID: 25713022
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