Telomere Length of Circulating Cell-Free DNA and Gastric Cancer in a Chinese Population at High-Risk

Abstract

Background: Telomeres have long been found to be involved in cancer development, while little was known about the dynamic changes of telomere length in carcinogenesis process. Methods: The present study longitudinally investigated telomere alterations of cell-free DNA (cfDNA) in 86 gastric cancer (GC) subjects recruited through a 16-year prospective cohort with 2-4 serums collected before each GC-diagnosis from baseline and three follow-up time-points (a total of 276 samples). As the control, 86 individual-matched cancer-free subjects were enrolled with 276 serums from the matched calendar year. Results: In the 73 pairs of baseline serums from GC and control subjects, shortened telomeres showed increased subsequent GC risk [odds ratio (OR) = 9.17, 95% CI: 2.72-31.25 for 1 unit shortening]. In each baseline gastric lesion category, higher risks of GC progression were also found with shortened cfDNA telomeres; ORs per 1 unit shortening were 6.99 (95% CI: 1.63-30.30) for mild gastric lesions, 6.06 (95% CI: 1.89-19.61) for intestinal metaplasia and 15.63 (95% CI: 1.91-125.00) for dysplasia. With all measurements from baseline and follow-up time-points, shortened telomeres also showed significant association with GC risk (OR = 7.37, 95% CI: 2.06-26.32 for 1 unit shortening). In temporal trend analysis, shortened telomeres were found in GC subjects compared to corresponding controls more than 3 years ahead of GC-diagnosis (most P < 0.05), while no significant difference was found between two groups within 3 years approaching to GC-diagnosis. Conclusion: Our findings suggest that telomere shortening may be associated with gastric carcinogenesis, which supports further etiological study and potential biomarker for risk stratification.

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

“…Given the well-established knowledge that shorter telomeres contribute to cellular senescence [72], both tTL and telomerase activity (TA) have been the subject of research on cancer-related biomarkers. In fact, an increasing body of evidence supports the potential of both serving as diagnostic and prognostic biomarkers for various cancers [73,74]. The underlying hypothesis is that when cellular senescence is combined with excessive environmental burden (for instance UV exposure), the cell may be led to apoptosis.…”

Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies

“…They found that its levels were significantly reduced in patients with no prior treatment when compared to control individuals, suggesting that plasma cf-telDNA levels are associated with breast cancer susceptibility [ 139 ]. In gastric cancer, shortened telomeres were associated with gastric cancer risk [ 134 ], while RTL was found to be significantly lower in endometrial cancer patients [ 135 ]. This data is in accordance with the existence of paradoxically shorter telomeres in patients with cancer.…”

The Utility of Repetitive Cell-Free DNA in Cancer Liquid Biopsies

“…Two further studies assessed cfDNA telomere length in gastric [ 90 ] and endometrial cancer [ 91 ]. In gastric cancer, with all measurements from baseline and different follow-up time-points, shortened telomeres were found to be significantly associated with gastric cancer risk (OR = 7.37, 95% CI: 2.06–26.32 for 1 unit shortening) [ 90 ].…”

“…Two further studies assessed cfDNA telomere length in gastric [ 90 ] and endometrial cancer [ 91 ]. In gastric cancer, with all measurements from baseline and different follow-up time-points, shortened telomeres were found to be significantly associated with gastric cancer risk (OR = 7.37, 95% CI: 2.06–26.32 for 1 unit shortening) [ 90 ]. Benati et al evaluated the diagnostic performance of relative telomere length (i.e., telomere repeat copy number to single-gene copy number ratio) in cfDNA and found RTL to be significantly lower in endometrial patients with cancer [ 91 ].…”