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

Grant Number: 5R03CA133914-02 Interpret this number
Primary Investigator: Han, Jiali
Organization: Brigham And Women'S Hospital
Project Title: Prospective Study of Telomere Length and Melanoma Risk
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): Abstract: Prospective study of telomere length and melanoma risk Telomere length in peripheral blood leukocytes (PBLs) has emerged as a potential biomarker of aging and of risk of age-related diseases such as cancers. Telomere length is determined in part by inherited genetic factors. In addition to causing DNA damage, UVB irradiation shortens telomeres. In skin tissue, telomere disruption triggers multiple DNA damage responses. We propose to examine telomere length and genetic variants in telomere-related genes in relation to the risk of cutaneous malignant melanoma (hereafter called melanoma). We will include 586 incident cases of melanoma and 586 matched controls who provided blood samples pre-diagnostically from three large well- characterized cohorts, the Women's Health Initiative Observational Study, the Nurses Health Study, and Nurses Health Study II. In addition, we will assess the interactions between telomere length and genetic variants in telomere-related genes and tendency to burn/tan on melanoma risk. This application will take advantage of the research opportunities nested within the existing well-characterized cohort, including cohort characteristics, quality of design, high follow-up rate, and large sample size. Our study will also take advantage of the previously confirmed cases of melanoma, stored blood and DNA samples, as well as previously collected information on host risk factors. To date, no one has evaluated how telomere length or genetic variation in telomere-related genes may influence melanoma risk. In this study, we will examine whether the risk of melanoma is higher in women with shorter telomeres and is influenced by variation in genes related to telomere stability and maintenance. Establishing the relationship between telomere length in pre-diagnostically collected peripheral blood leukocytes and melanoma risk will be important for several reasons. It would provide corroboration for the hypothesis that biological processes related to aging are important determinants of melanoma risk and may provide an assay to be used part of an assessment of melanoma risk. This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies. Project Narrative: We propose a prospective evaluation of telomere length and the genetic variants in telomere-related genes in relation to the risk of cutaneous malignant melanoma. Establishing the relationship between telomere length in pre-diagnostically collected peripheral blood leukocytes and melanoma risk will be important for several reasons. It would provide corroboration for the hypothesis that biological processes related to aging are important determinants of melanoma risk and may provide an assay to be used part of an assessment of melanoma risk. This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies.

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Publications

Mediterranean Diet And Telomere Length In Nurses' Health Study: Population Based Cohort Study
Authors: Crous-Bou M. , Fung T.T. , Prescott J. , Julin B. , Du M. , Sun Q. , Rexrode K.M. , Hu F.B. , De Vivo I. .
Source: Bmj (clinical Research Ed.), 2014; 349, p. g6674.
PMID: 25467028
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Genetic Predisposition To Higher Body Mass Index Or Type 2 Diabetes And Leukocyte Telomere Length In The Nurses' Health Study
Authors: Du M. , Prescott J. , Cornelis M.C. , Hankinson S.E. , Giovannucci E. , Kraft P. , De Vivo I. .
Source: Plos One, 2013; 8(2), p. e52240.
PMID: 23424613
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Paternal Age At Birth Is Associated With Offspring Leukocyte Telomere Length In The Nurses' Health Study
Authors: Prescott J. , Du M. , Wong J.Y. , Han J. , De Vivo I. .
Source: Human Reproduction (oxford, England), 2012 Dec; 27(12), p. 3622-31.
PMID: 22940768
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Shorter Telomeres Associate With A Reduced Risk Of Melanoma Development
Authors: Nan H. , Du M. , De Vivo I. , Manson J.E. , Liu S. , McTiernan A. , Curb J.D. , Lessin L.S. , Bonner M.R. , Guo Q. , et al. .
Source: Cancer Research, 2011-11-01 00:00:00.0; 71(21), p. 6758-63.
PMID: 22028319
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No Association Between Telomere Length In Peripheral Blood Leukocytes And The Risk Of Nonmelanoma Skin Cancer
Authors: Liang G. , Qureshi A.A. , Guo Q. , De Vivo I. , Han J. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2011 May; 20(5), p. 1043-5.
PMID: 21357377
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Genetic Variants In Telomere-maintaining Genes And Skin Cancer Risk
Authors: Nan H. , Qureshi A.A. , Prescott J. , De Vivo I. , Han J. .
Source: Human Genetics, 2011 Mar; 129(3), p. 247-53.
PMID: 21116649
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Genome-wide Association Study Of Relative Telomere Length
Authors: Prescott J. , Kraft P. , Chasman D.I. , Savage S.A. , Mirabello L. , Berndt S.I. , Weissfeld J.L. , Han J. , Hayes R.B. , Chanock S.J. , et al. .
Source: Plos One, 2011; 6(5), p. e19635.
PMID: 21573004
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Associations Between Rotating Night Shifts, Sleep Duration, And Telomere Length In Women
Authors: Liang G. , Schernhammer E. , Qi L. , Gao X. , De Vivo I. , Han J. .
Source: Plos One, 2011; 6(8), p. e23462.
PMID: 21853136
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A Prospective Study Of Telomere Length And The Risk Of Skin Cancer
Authors: Han J. , Qureshi A.A. , Prescott J. , Guo Q. , Ye L. , Hunter D.J. , De Vivo I. .
Source: The Journal Of Investigative Dermatology, 2009 Feb; 129(2), p. 415-21.
PMID: 18668136
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