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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Leukocyte Telomere Length and Its Interaction with Germline Variation in Telomere-Related Genes in Relation to Pancreatic Adenocarcinoma Risk

Samuel O. Antwi, William R. Bamlet, Kari G. Rabe, Richard M. Cawthon, Isoken Umudi, Brooke R. Druliner, Hugues Sicotte, Ann L. Oberg, Aminah Jatoi, Lisa A. Boardman and Gloria M. Petersen
Samuel O. Antwi
1Division of Epidemiology, Mayo Clinic, Jacksonville, Florida.
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  • For correspondence: Antwi.samuel@mayo.edu
William R. Bamlet
2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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  • ORCID record for William R. Bamlet
Kari G. Rabe
2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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Richard M. Cawthon
3Department of Human Genetics, University of Utah, Salt Lake City, Utah.
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Isoken Umudi
1Division of Epidemiology, Mayo Clinic, Jacksonville, Florida.
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Brooke R. Druliner
4Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Hugues Sicotte
2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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Ann L. Oberg
2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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Aminah Jatoi
4Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Lisa A. Boardman
4Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Gloria M. Petersen
5Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
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DOI: 10.1158/1055-9965.EPI-19-1597 Published July 2020
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Abstract

Background: Leukocyte telomere length (LTL) has been associated with risk of multiple cancers, but its association with pancreatic ductal adenocarcinoma (PDAC) is unclear. We therefore investigated the association between peripheral blood LTL and PDAC risk, and examined effect modification by candidate SNPs previously reported to be associated with variation in LTL.

Methods: A case–control study of 1,460 PDAC cases and 1,459 frequency-matched controls was performed using biospecimens and data from the Mayo Clinic Biospecimen Resource for Pancreas Research. Quantitative PCR was used to measure LTL and categorized into tertiles based on sex-specific control distribution. Eleven telomere-related SNPs also were genotyped. Logistic regression was used to calculate ORs and 95% confidence intervals (CI).

Results: Shorter peripheral blood LTL was associated with a higher risk of PDAC (ORT1vsT3 = 1.26, 95% CI = 1.03–1.54, Ptrend = 0.02; ORcontinuous = 1.14, 95% CI = 1.02–1.28), but the association was restricted to cases with treatment-naïve blood samples (ORT1vsT3 = 1.51, 95% CI = 1.16–1.96, Ptrend = 0.002; ORcontinuous = 1.25, 95% CI = 1.08–1.45) and not cases whose blood samples were collected after initiation of cancer therapy (ORT1vsT3 = 1.10, 95% CI = 0.87–1.39, Ptrend = 0.42; ORcontinuous = 1.08, 95% CI = 0.94–1.23). Three SNPs (TERC-rs10936599, ACYP2-rs11125529, and TERC-rs1317082) were each associated with interindividual variation in LTL among controls, but there was no evidence of effect modification by these SNPs.

Conclusions: Treatment-naïve short LTL is associated with a higher risk of PDAC, and the association does not differ by germline variation in the candidate telomere-related SNPs examined.

Impact: Peripheral blood LTL might serve as a molecular marker for risk modeling to identify persons at high risk of PDAC.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2020;29:1492–500

  • Received December 24, 2019.
  • Revision received March 18, 2020.
  • Accepted April 15, 2020.
  • Published first April 20, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 29 (7)
July 2020
Volume 29, Issue 7
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Leukocyte Telomere Length and Its Interaction with Germline Variation in Telomere-Related Genes in Relation to Pancreatic Adenocarcinoma Risk
Samuel O. Antwi, William R. Bamlet, Kari G. Rabe, Richard M. Cawthon, Isoken Umudi, Brooke R. Druliner, Hugues Sicotte, Ann L. Oberg, Aminah Jatoi, Lisa A. Boardman and Gloria M. Petersen
Cancer Epidemiol Biomarkers Prev July 1 2020 (29) (7) 1492-1500; DOI: 10.1158/1055-9965.EPI-19-1597

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Leukocyte Telomere Length and Its Interaction with Germline Variation in Telomere-Related Genes in Relation to Pancreatic Adenocarcinoma Risk
Samuel O. Antwi, William R. Bamlet, Kari G. Rabe, Richard M. Cawthon, Isoken Umudi, Brooke R. Druliner, Hugues Sicotte, Ann L. Oberg, Aminah Jatoi, Lisa A. Boardman and Gloria M. Petersen
Cancer Epidemiol Biomarkers Prev July 1 2020 (29) (7) 1492-1500; DOI: 10.1158/1055-9965.EPI-19-1597
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