Study
PLCO
(Learn more about this study)
Project ID
2007-0218
Initial CDAS Request Approval
Dec 20, 2007
Title
Telomere length as a Risk Factor for Pancreatic Cancer
Summary
Exocrine pancreatic cancer is among the most fatal cancers worldwideand one for which few preventable risk factors have been established(e.g., smoking, diabetes mellitus and obesity). Telomeres are structures at the end of chromosomes that are critical in maintaining the integrity of the genome by protecting against chromosomal break-fusion-bridge cycles in dividing cells. Telomere length shortening is an early event in tumorigenesis for most human epithelial cancers and has been observed pancreatic intraepithelial neoplasms or PanIN which are early precursors of pancreatic adenocarcinoma. Recent studies have shown that peripheral blood cell (PBC) DNA telomere length in normal somatic cells of healthy individuals may be a predictive marker for disease, including heart disease, insulin resistance, and cancer. We propose to conduct a nested case-control (131 cases and 393 matched controls) study within the PLCO Trial using DNA extracted from T0 blood samples (buffy coat) to examine whether telomere length measured in PBCs is prospectively associated with pancreatic cancer. We hypothesize that shorter telomere length in normal somatic cells (i.e., PBCs) may be a risk factor for pancreatic cancer. We will also evaluate exogenous and endogenous predictors of telomere length in PBC. The PLCO Trial cohort provides an opportunity to test these relationships in a prospective setting, avoiding the biases of retrospective research, in particular reverse-causation bias. Others in DCEG have already carried out pilot work, establishing the reproducibility of the assays. The results from this study may provide insight into the mechanisms related to pancreatic carcinogenesis and may have important implications for the prevention of pancreatic cancer.
Aims
This proposed nested case-control study within the PLCO study cohort aims to examine whether telomere length measured in PBCs is prospectively associated with pancreatic cancer. The primary aim of this study is: 1. To test the hypothesis that telomere length in normal somatic cells (i.e., PBCs) is associated with pancreatic cancer. We hypothesize that shorter telomere length will be positively associated with pancreatic cancer. The secondary aim of this study is: To evaluate exogenous (diet, smoking history, diabetes history, obesity, and environmental) and endogenous (c-peptide, CRP, IGF-axis biomarkers, vitamin D status) exposures as predictors of telomere length in PBCs. To evaluate effect modification of the association between telomere length in PBC and pancreatic cancer by smoking history, obesity, diet, and other biomarkers measure in preceding pancreatic cancer studies conducted in the PLCO cohort.
Collaborators
Mitch Gail (Biostatistics Branch)
Richard Hayes (Occupational Epidemiology Branch)
Immaculata DeVivo (Harvard University)
Rachael Stolzenberg-Solomon (NCI, DCEG)
