Abstract
BackgroundHuman telomeres, tandem repeats of TTAGGG nucleotides at the ends of chromosomes, are essential for maintaining genomic integrity and stability. Results of previous epidemiologic studies about the association of telomere length with risk of colorectal cancer (CRC) have been conflicting.MethodsA case-control study was conducted in a Han population in Wuhan, central China. The relative telomere length (RTL) was measured in peripheral blood leukocytes (PBLs) using quantitative real-time polymerase chain reaction (PCR) in 628 CRC cases and 1,256 age and sex frequency matched cancer-free controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression models to evaluate the association between RTL and CRC risk.ResultsUsing median RTL in the controls as the cutoff, individuals with shorter RTL were associated with a significantly increased risk of CRC (adjusted OR = 1.27, 95%CI: 1.05–1.55). When participants were further categorized into 3 and 4 groups according to the tertile and quartile RTL values of controls, significant relationships were still observed between shorter RTL and increased CRC risk (OR per tertile = 1.13, 95%CI: 1.00–1.28, P trend = 0.045; OR per quartile = 1.12, 95%CI: 1.03–1.23, P trend = 0.012). In stratified analyses, significant association between shorter RTL and increased CRC risk was found in females, individuals younger than 60 years old, never smokers and never drinkers.ConclusionsThis study suggested that short telomere length in PBLs was significantly associated with an increased risk of CRC in Chinese Han population. Further validation in large prospective studies and investigation of the biologic mechanisms are warranted.
Highlights
Human telomeres are tandem repeats of TTAGGG nucleotides that cap the ends of the eukaryotic chromosome arms[1,2]
There were no significant differences in the distribution of age, sex and body mass index (BMI) between cases and controls
We found a significant association between shorter relative telomere length (RTL) and increased colorectal cancer (CRC) risk in females (OR = 1.72, 95% confidence interval. aAdjusted by age (CI): 1.28–2.31) and individuals younger than 60 years old (OR = 1.39, 95% confidence intervals (95% CI): 1.06–1.83), but not in males and participants older than 60 years old (Table 3)
Summary
Human telomeres are tandem repeats of TTAGGG nucleotides that cap the ends of the eukaryotic chromosome arms[1,2]. Human telomeres are approximately 10– 15 kb and progressively shortened by 30 to 200 base pairs after each cycle of mitotic division, due to the‘‘end replication problem’’ and the absence of a mechanism for elongation of telomeres[5,6,7]. If apoptosis does not happen and cell division continues, the resultant genomic instability will lead to chromosomal abnormalities. Lack of normal DNA damage response mechanisms, continue to divide despite critically short telomeres by utilizing the alternative telomeres prolongation mechanism or upregulating of telomerase[15,16]. Tandem repeats of TTAGGG nucleotides at the ends of chromosomes, are essential for maintaining genomic integrity and stability. Results of previous epidemiologic studies about the association of telomere length with risk of colorectal cancer (CRC) have been conflicting
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