Abstract 2360: Association of telomere length with colorectal cancer risk and prognosis: A systematic review and meta-analysis

Abstract

Abstract Background: Telomeres are repetitive nucleotide structures at the end of eukaryotic chromosomes. Both shortened as well as elongated telomeres can cause chromosomal instability, thereby influencing the risk and prognosis of several cancers, including colorectal cancer. Methods: We performed a systematic review and meta-analysis of published studies to quantitatively assess the association of telomere length with colorectal cancer risk and survival. Following the PRISMA guidelines and using relevant MeSH terms, we searched PubMed, EMBASE, and Web of Science databases through November 20, 2019 to identify full-text English articles investigating the association of telomere length with colorectal cancer risk and survival. Odds ratios (OR), hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted from the included studies. As the model parametrization differed across studies, we converted all effect estimates into ORs for longest vs shortest quartile. Using the R software “meta”, we calculated overall risk estimates and 95% CIs using a random-effects model and assessed the inter-study heterogeneity using the Cochrane's Q- test and the I2- statistic. Potential publication bias was assessed by constructing a funnel plot. Results: Of the 385 articles identified from the three databases, 12 studies from Europe, Asia and the United States were eligible for meta-analysis (risk: 8 case-control studies; survival: 4 cohort studies), contributing a total of 34,120 patients for risk analysis and 1,247 patients for survival analysis. In risk-related meta-analysis, we did not observe evidence of an association between leukocyte telomere length and risk of colorectal cancer [overall OR (95% CI): 1.02 (0.96-1.08), P-value =0.50]. This lack of evidence of a relationship did not change even after excluding the two studies with a U-shaped pattern of association between telomere length and risk. Substantial heterogeneity among included studies (I2=68% and Q-test p<0.01) was observed. In meta-analysis for survival, we did not observe conclusive evidence of an association between telomere length and overall or disease-free survival [OS: overall HR (95% CI) =1.72 (0.95-3.13); DFS: overall HR (95% CI) =0.78 (0.18-3.39)]. There was also substantial heterogeneity observed among studies on survival (Q-test p= 0.33, I2-statistic 86%). No evidence of publication bias was observed on funnel plots. Discussion: This meta-analysis did not provide conclusive evidence of an association between telomere length and colorectal cancer risk or survival, though the number of published studies on survival are limited. Future larger studies, evaluating a potentially non-linear relationship between telomeres and colorectal cancer and accounting for age, are required to better understand the role of telomeres in colorectal cancer etiology and progression. Citation Format: Svenja Pauleck, Jennifer Sinnot, Richard Viskochil, Benjamin Haaland, Sheetal Hardikar. Association of telomere length with colorectal cancer risk and prognosis: A systematic review and meta-analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2360.