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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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Abstract

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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Publications

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth.
Authors: Titus LJ, Clough-Gorr K, Mackenzie TA, Perry A, Spencer SK, Weiss J, Abrahams-Gessel S, Ernstoff MS
Source: Br J Dermatol, 2013 Mar;168(3), p. 571-6.
EPub date: 2012 Oct 5.
PMID: 22897437
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Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls.
Authors: Chang YM, Barrett JH, Bishop DT, Armstrong BK, Bataille V, Bergman W, Berwick M, Bracci PM, Elwood JM, Ernstoff MS, Gallagher RP, Green AC, Gruis NA, Holly EA, Ingvar C, Kanetsky PA, Karagas MR, Lee TK, Le Marchand L, Mackie RM, Olsson H, Østerlind A, Rebbeck TR, Sasieni P, Siskind V, Swerdlow AJ, Titus-Ernstoff L, Zens MS, Newton-Bishop JA
Source: Int J Epidemiol, 2009 Jun;38(3), p. 814-30.
EPub date: 2009 Apr 8.
PMID: 19359257
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Factors associated with atypical moles in New Hampshire, USA.
Authors: Titus-Ernstoff L, Ding J, Perry AE, Spencer SK, Cole BF, Ernstoff MS
Source: Acta Derm Venereol, 2007;87(1), p. 43-8.
PMID: 17225015
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Multiple primary melanoma: two-year results from a population-based study.
Authors: Titus-Ernstoff L, Perry AE, Spencer SK, Gibson J, Ding J, Cole B, Ernstoff MS
Source: Arch Dermatol, 2006 Apr;142(4), p. 433-8.
PMID: 16618861
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Pigmentary characteristics and moles in relation to melanoma risk.
Authors: Titus-Ernstoff L, Perry AE, Spencer SK, Gibson JJ, Cole BF, Ernstoff MS
Source: Int J Cancer, 2005 Aug 10;116(1), p. 144-9.
PMID: 15761869
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