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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA133914-02
Application #
7615730
Study Section
Special Emphasis Panel (ZCA1-SRRB-D (J1))
Program Officer
Martin, Damali
Project Start
2008-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$87,608
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Mons, Ute; Müezzinler, Aysel; Schöttker, Ben et al. (2017) Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies. Am J Epidemiol 185:1317-1326
Crous-Bou, Marta; Fung, Teresa T; Prescott, Jennifer et al. (2014) Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study. BMJ 349:g6674
Du, Mengmeng; Prescott, Jennifer; Cornelis, Marilyn C et al. (2013) Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study. PLoS One 8:e52240
Prescott, J; Du, M; Wong, J Y Y et al. (2012) Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study. Hum Reprod 27:3622-31
Nan, Hongmei; Du, Mengmeng; De Vivo, Immaculata et al. (2011) Shorter telomeres associate with a reduced risk of melanoma development. Cancer Res 71:6758-63
Nan, Hongmei; Qureshi, Abrar A; Prescott, Jennifer et al. (2011) Genetic variants in telomere-maintaining genes and skin cancer risk. Hum Genet 129:247-53
Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I et al. (2011) Genome-wide association study of relative telomere length. PLoS One 6:e19635
Liang, Geyu; Qureshi, Abrar A; Guo, Qun et al. (2011) No association between telomere length in peripheral blood leukocytes and the risk of nonmelanoma skin cancer. Cancer Epidemiol Biomarkers Prev 20:1043-5
Liang, Geyu; Schernhammer, Eva; Qi, Lu et al. (2011) Associations between rotating night shifts, sleep duration, and telomere length in women. PLoS One 6:e23462
Han, Jiali; Qureshi, Abrar A; Prescott, Jennifer et al. (2009) A prospective study of telomere length and the risk of skin cancer. J Invest Dermatol 129:415-21