Epidemiologic evidence for a role of telomere dysfunction in cancer etiology.

Telomeres, the dynamic nucleoprotein structures at the ends of linear chromosomes, maintain the genomic integrity of a cell. Telomere length shortens with age due to the incomplete replication of DNA ends with each cell division as well as damage incurred by oxidative stress. Patterns of telomere shortening, genomic instability, and telomerase expression in many cancer tissues compared to adjacent normal tissue implicate telomere crisis as a common crucial event in malignant transformation. In order to understand the role of telomere length in cancer etiology, most epidemiologic studies have measured average telomere length of peripheral blood or buccal cell DNA as a surrogate tissue biomarker of telomere dysfunction and cancer risk. In this review, we present the results from epidemiologic investigations conducted of telomere length and cancer risk. We note differences in reported associations based on study design, which may be due to biases intrinsic to retrospective studies. Finally, we conclude with study design considerations as future investigations are needed to elucidate the relationship between telomere length and a number of cancer sites.