Leukocyte Telomere Length and Cancer Risk: A Dynamic Problem

Telomeres are the protective structure at both ends of each chromoThe decelerating age-adjusted LTL attrition in cancer cases as they some. Telomere length is widely considered a marker of biological aging. For convenience, telomere lengths in human population studies have been predominately measured in peripheral blood leukocytes. Although leukocyte telomere length (LTL) is generally inversely correlated with age, there is considerable inter-individual variation of LTL among people of the same ages (Aubert and Lansdorp, 2008). An individual's LTL at any given age is determined by a combination of genetic, environmental, and lifestyle factors (Lin et al., 2012). The interindividual variation of LTL has been proposed to contribute to an individual's susceptibility to age-related diseases, including cancer. Since the first epidemiologic study linking short LTL with increase risks of several cancers in 2003 (Wu et al., 2003), there have been numerous studies assessing the association of LTL with the risks of cancer (Weischer et al., 2013;Wentzensen et al., 2011), but the resultswere inconsistent. The inconsistent results are often attributed to technical variations in LTL measurement methods, “reverse causation” limitation in retrospective case control studies, small sample size of cancer cases in prospective cohort studies, and heterogeneous populations. Furthermore, all the published studies relating LTL to cancer risks have used a single time measurement of LTL without consideration of longitudinal changes of LTL. In this issue of EBioMedicine, Hou et al. (2015), for the first time, reported a dynamic change of LTL in the context of cancer risks. This study included 792 Normative Aging Study participants with one to four LTL measurements during a follow-up of 12-years. The authors observed that age-related LTL attrition was accelerated among participants who ultimately developed cancer. Strikingly, this trend reversed when age-adjusted LTL was examined relative to time to diagnosis. This divergence of age-adjusted LTL attrition began seven years pre-diagnosis and culminated in significantly longer LTL 3– 4 years pre-diagnosis among cancer cases compared to cancer-free participants, resulting in a positive association between longer LTL measured within 4 years of diagnosis and increased risks of prostate cancer and all cancers combined. This provocative observation provides important biological insight into the role of the telomeres in cancer etiology and adds another possible explanation to the prior inconsistencies in reporting the association of LTL with cancer risks.