Telomeres in Gastrointestinal Cancers

DNA repeats and protective proteins, which comprise telomere complexes, are crucial for genomic integrity; however, the inherent limitations of DNA end-replication through cell divisions lead to age-dependent telomere shortening. Telomere attrition, besides being a quintessential characteristic of aging, acts as a natural tumor suppressor mechanism by inhibiting unlimited cell division. Constitutive telomere length, a heritable trait, is associated with various cancers. Oxidative DNA damage and replicative stress, driven by genetic, epigenetic, and environmental factors, also contribute to telomere shortening. Besides, telomere maintenance dynamics within tumors and within cells in the tumor microenvironment critically influence outcomes in different cancers. Within tumors, despite activated elongation mechanisms, various functional constraints result in short telomeres, indicating a crucial role for telomere biology components in cancer outcomes. In this review, we explored the telomere length in leucocytes and cancer tissues in relation to risk and survival in major gastrointestinal cancers, including colorectal, pancreatic, and esophageal cancers.