The role of Telomere length in the risk of colorectal cancer incidence: A cohort study from the Singapore Chinese Health StudyQi, Meiyuzhen (2018) The role of Telomere length in the risk of colorectal cancer incidence: A cohort study from the Singapore Chinese Health Study. Master Essay, University of Pittsburgh.
AbstractBackground: Telomeres are repeated DNA sequences at the end of chromosomes. Each cell division causes telomere shortening. Under normal circumstance, when telomeres are shortened to a critical level, the programmed cell death or apoptosis mechanism is invoked and results in cell death. However, some rare cells, even with extremely short telomeres, escape the apoptosis pathway with sustaining proliferation, a hall marker of cancer. Therefore, telomeres may play an important role in the development and progression of cancer. However, despite the public health significance of colorectal cancer, there is a lack of consensus about the association between telomere length and colorectal cancer. Objective: The present study was to prospectively examine the association between telomere length and the risk of developing colorectal cancer. Methods: We obtained blood sample from 26,761 cancer-free participants at baseline in Singapore Chinese Health Study between April 1994 and April 2005. Telomere length in leukocytes was quantified using monochrome qPCR. Until December 31, 2008, 347 subjects developed colorectal cancer (209 colon cancer and 138 rectal cancer). Multivariate Cox proportional hazard regression models were used to estimate hazard ratio (HR) and their 95% confidence interval (CI) of for risk of colon, rectal and colorectal cancer associated with longer telomeres compared with shorter telomeres after adjusting for multiple covariates. Results: Subjects with highest quartile of telomere length had a statistically significant 55% increased risk of colorectal cancer (HR=1.55, 95% CI: 1.14-2.10) compared with the lowest quartile of telomere length after adjusting for potential confounders (p-trend=0.013). This positive association became stronger (HR=1.70, 95% CI: 1.16-2.48) after excluding patients who were diagnosed with colorectal cancer within the first two years post blood collection (p-trend=0.022). A statistically significant and stronger association between telomere length and risk of colorectal cancer was observed among never smokers and participants without history of diabetes. Conclusion: This large cohort study built on Singapore Chinese population provides new evidence that longer telomere is associated with a higher risk of colorectal cancer, particularly among those who never smoked cigarettes or had no history of diabetes. Further studies are needed to explain the involved biologic mechanisms. Share
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