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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


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.



Publications

Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies.
Authors: Mons U. , Müezzinler A. , Schöttker B. , Dieffenbach A.K. , Butterbach K. , Schick M. , Peasey A. , De Vivo I. , Trichopoulou A. , Boffetta P. , et al. .
Source: American journal of epidemiology, 2017-06-15; 185(12), p. 1317-1326.
PMID: 28459963
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Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.
Authors: Liu J.J. , Crous-Bou M. , Giovannucci E. , De Vivo I. .
Source: The Journal of nutrition, 2016 Jul; 146(7), p. 1373-8.
EPub date: 2016-06-08.
PMID: 27281805
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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.), 2014-12-02; 349, p. g6674.
EPub date: 2014-12-02.
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.
EPub date: 2013-02-12.
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.
EPub date: 2012-08-30.
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; 71(21), p. 6758-63.
EPub date: 2011-10-25.
PMID: 22028319
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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, 2011-05-10; 6(5), p. e19635.
EPub date: 2011-05-10.
PMID: 21573004
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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.
EPub date: 2011-02-25.
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.
EPub date: 2010-11-30.
PMID: 21116649
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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.
EPub date: 2011-08-10.
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.
EPub date: 2008-07-31.
PMID: 18668136
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