4.6 Article

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

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FRONTIERS IN ONCOLOGY
卷 9, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2019.01434

关键词

cell-free DNA; prospective cohort; gastric cancer; serum; telomere length

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资金

  1. Beijing Science Technology Commission [Z151100001615022]
  2. National Basic Research Program of China [2010CB529303]
  3. National Key Technology Research and Development Program [2015BA13B07]
  4. Science Foundation of Peking University Cancer Hospital [2017-6]
  5. Beijing Municipal Administration of Hospitals' Ascent Plan [DFL20181102]
  6. Beijing Natural Science Foundation [7182032]

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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.

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