Svenja Pauleck1, Biljana Gigic2, Richard M Cawthon3, Jennifer Ose4, Anita R Peoples4, Christy A Warby4, Jennifer A Sinnott5, Tengda Lin4, Juergen Boehm6, Petra Schrotz-King7, Christopher I Li8, David Shibata9, Erin M Siegel10, Jane C Figueiredo11, Adetunji T Toriola12, Martin Schneider2, Alexis B Ulrich2, Albrecht Hoffmeister13, Cornelia M Ulrich4, Sheetal Hardikar14. 1. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; University of Leipzig Medical Center, Medical Faculty, Leipzig, Germany. 2. Heidelberg University Hospital, Heidelberg, Germany; National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA. 4. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. 5. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA; Department of Pediatrics, University of Utah, Salt Lake City, UT, USA; Department of Statistics, The Ohio State University, Columbus, OH, USA. 6. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. 7. National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany. 8. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 9. University of Tennessee Health Science Center, Memphis, TN, USA. 10. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. 11. Cedars-Sinai Medical Center, Los Angeles, CA, USA. 12. Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA. 13. Medical Department II, Division of Gastroenterology, University of Leipzig Medical Center, Leipzig, Germany. 14. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: sheetal.hardikar@hci.utah.edu.
Abstract
INTRODUCTION: Telomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer. METHODS: Baseline genomic DNA from blood leukocytes was extracted from N = 92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing. RESULTS: The mean T/S ratio for study patients was 0.5 (range: 0.3-0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p = 0.31) and disease-free survival (long-rank p = 0.23). CONCLUSIONS: Our results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression.
INTRODUCTION: Telomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer. METHODS: Baseline genomic DNA from blood leukocytes was extracted from N = 92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing. RESULTS: The mean T/S ratio for study patients was 0.5 (range: 0.3-0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p = 0.31) and disease-free survival (long-rank p = 0.23). CONCLUSIONS: Our results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression.
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