Article Text

other Versions

PDF
Telomere length and pancreatic cancer risk: breaking down the evidence
  1. Eric J Duell
  1. Correspondence to Dr Eric J Duell, Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Avda Gran Via 199-203, L'Hospitalet de Llobregat, Barcelona 08908, Spain; eduell{at}iconcologia.net

Statistics from Altmetric.com

Telomeres, located at the ends of chromosomes and composed of a protein complex and tandem repeats of TTAGGG nucleotides, function to protect chromosomes from end-to-end fusions, breakage and degradation in dividing cells. Due to the inherent nature of DNA replication (‘the end replication problem’) and oxidative stress—telomeres gradually shorten with age. This has been demonstrated cross-sectionally in most tissues examined including the pancreas, and especially in cells with extensive proliferation (eg, leucocytes).1 ,2 Cells with critically short telomeres enter growth arrest, or senescence, and may remain viable for extended periods. Premalignant cells can avoid senescence and continue to proliferate by upregulating telomerase or elongating telomeres by alternative mechanisms.1

Shortened telomeres are thought to contribute to chromosomal instability and age-related diseases in humans, including cancer. Up to 90% of human tumours reactivate telomerase, which is epigenetically silenced in most adult somatic cells.1 Somatic promoter mutations and germ-line sequence variants at TERT (the gene that encodes the catalytic subunit of telomerase reverse transcriptase on chr 5p15.33) have been observed in various human cancers, indicating extensive pleiotropy at this locus.3 Although somatic mutations in TERT are uncommon in pancreatic cancer (PC), several independent PC risk loci marked by common (and less common) susceptibility alleles have been (and likely will continue to be) identified at the …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Pancreas
    Ying Bao Jennifer Prescott Chen Yuan Mingfeng Zhang Peter Kraft Ana Babic Vicente Morales-Oyarvide Zhi Rong Qian Julie E Buring Barbara B Cochrane J Michael Gaziano Edward L Giovannucci JoAnn E Manson Kimmie Ng Shuji Ogino Thomas E Rohan Howard D Sesso Meir J Stampfer Charles S Fuchs Immaculata De Vivo Laufey T Amundadottir Brian M Wolpin