Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at 5 years after diagnosis. In the last 15 years, telomere length (TL) measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere-associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk?