The Effect of Cancer Treatments on Telomere Length: A Systematic Review of the Literature

Abstract

Background: It has been hypothesized that cancer treatments cause accelerated aging through a mechanism involving the shortening of telomeres. However, the effect of cancer treatments on telomere length is unclear. Methods: We systematically reviewed the epidemiological evidence evaluating the associations between cancer treatment and changes in telomere length. Searches were performed in PubMed for the period of January 1966 through November 2016 using the following search strategy: telomere AND (cancer OR tumor OR carcinoma OR neoplasm) AND (survivor OR patient). Data were extracted and the quality of studies was assessed. Results: A total of 25 studies were included in this review. Ten were solid cancer studies, 11 were hematological malignancy studies, and 4 included a mixed sample of both solid and hematological cancers. Three of the 10 solid tumor studies reported a statistically significant association between cancer treatment and telomere length shortening, and one reported longer telomere length after treatment. Among the hematological cancer studies, three showed statistically significant decreases in telomere length with treatment, and two showed elongation. When these studies were rated using quality criteria, most of the studies were judged to be of moderate quality. Conclusions: The findings from this review indicate that the effect of cancer treatment on telomere length may differ by cancer type and treatment as well as other factors. Definitive conclusions cannot be made based on the published literature, because sample sizes tended to be small; treatments, cancer types, and biospecimens were heterogenous; and the length of follow-up times differed greatly. REVIEW

Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort

“…Not all LTL variability can be attributed directly to age, however. LTL is highly heritable (6)(7)(8), differs by gender (9), and is associated with health behaviors (10)(11)(12)(13)(14) including smoking, alcohol intake, diet, and physical activity, shared environmental factors in twins (15) and cancer treatment modalities and doses (16,17) including chemotherapy and radiation therapy (RT). LTL is also associated with age-related diseases (18,19), including cancers (20,21) and cardiovascular diseases (22,23).…”

Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study

“…Few investigators have evaluated chromosome-specific telomere lengths as they relate to cancer and/or chemotherapy, with the few reported studies focusing on the relationship between chromosome-specific length and the risk of acquiring BC or esophageal cancer (Additional File 8). In their review of the effects of cancer treatment on telomere lengths, Gallicchio et al [11] noted conflicting results between studies, with the observed variations reflecting differences in study designs/ methodologies, as well as treatment regimens. The results of our investigation underscore the value of assessing telomere length using a longitudinal study design and using a telomere assay that provides estimates of individual telomeres, rather than a genomic "average" length (Additional File 8).…”

“…Potential relationship between chromosome-specific telomere values and cognitive domains were also assessed using a model wherein each individual telomere was evaluated separately. This analytic approach showed significant relationships between visual memory domain scores and individual telomeres localized to (a) the long arm of chromosomes 1,2,3,4,6,7,8,10,11,12,13,15,16,18,20,22, and X and (b) the short arm of chromosomes 3,7,8,10,11,13,14,15,16,17,18,and 19 (Additional File 7]). However, no significant associations were detected for other cognitive domains.…”

“…Telomere length alterations in patients with BC have been evaluated as a diagnostic marker in breast tissues, but few investigators have evaluated the effect of chemotherapy on the telomere lengths of healthy, peripheral tissues in these patients [11]. Based on the scientific premise that telomere shortening is accelerated by inflammation and oxidative stress, and that chemotherapy affects both of these biological processes, the primary objective of this study was to longitudinally evaluate telomere length in women receiving treatment for BC over a 2-year period.…”

Genetic Variants of the TERT Gene, Telomere Length, and Circulating TERT as Prognostic Markers in Rectal Cancer Patients

“…This finding may suggest that a longer telomere could be more exposed to the effects of radiation and drugs employed during CRT. Several studies have shown that chemotherapeutic drugs induce the shortening of constitutive telomeres in peripheral blood cells [29,30]. It has been shown that the toxicity induced by 5-fluorouracil (5-FU) on hematopoietic cells was associated with a shortening of telomere length in peripheral blood mononuclear cells [31].…”