Telomere Length and Pancreatic Cancer: A Case–Control Study

Telomere Length and Pancreatic Cancer: A Case–Control Study

1. Halcyon G. Skinner1,2,
2. Ronald E. Gangnon1,2,3,
3. Kristin Litzelman1,
4. Ruth A. Johnson4,
5. Suresh T. Chari5,
6. Gloria M. Petersen6, and
7. Lisa A. Boardman5

+ Author Affiliations

1. Authors' Affiliations: ¹Department of Population Health Sciences; ²University of Wisconsin Carbone Cancer Center; ³Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, Wisconsin; Department of ⁴Laboratory Medicine and Pathology; ⁵Division of Gastroenterology and Hepatology; and ⁶Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota

1. Corresponding Author:
   Lisa A. Boardman, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Phone: 507-266-4338; Fax: 507-266-0350; E-mail: boardman.lisa@mayo.edu

Abstract

Background: Telomeres, the ends of chromosomes, are critical for maintaining genomic stability and grow shorter with age. Shortened telomeres in pancreatic tissue play a key role in the pathogenesis of pancreatic cancer, and shorter telomeres in peripheral blood leukocytes (PBL) have been associated with increased risk for several cancer types. We hypothesized that shorter blood telomeres are associated with higher risk for pancreatic cancer.

Methods: Telomere length was measured in PBLs using quantitative real-time PCR in 499 cases with pancreatic cancer and 963 cancer-free controls from the Mayo Clinic. ORs and confidence intervals (CI) were computed using logistic generalized additive models (GAM) adjusting for multiple variables.

Results: In multivariable adjusted models, we observed a significant nonlinear association between telomere length in peripheral blood samples and the risk for pancreatic cancer. Risk was lower among those with longer telomeres compared with shorter telomeres across a range from the 1st percentile to 90th percentile of telomere length. There was also some evidence for higher risk among those with telomeres in the longest extreme.

Conclusions: Short telomeres in peripheral blood are associated with an increased risk for pancreatic cancer across most of the distribution of length, but extremely long telomeres may also be associated with higher risk.

Impact: Although the temporality of this relationship is unknown, telomere length may be useful as either a marker of pancreatic cancer risk or of the presence of undetected pancreatic cancer. If telomere shortening precedes cancer incidence, interventions to preserve telomere length may be an effective strategy to prevent pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 21(11); 2095–100. ©2012 AACR.

• Received June 5, 2012.
• Revision received July 26, 2012.
• Accepted August 22, 2012.

• ©2012 American Association for Cancer Research.