Abstract
BACKGROUND: Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Abnormal alteration of telomere length has been linked to several cancers; however, epidemiologic evidence about the association of telomere length with colorectal cancer risk has been conflicting. METHODS: We conducted a nested case-control study to evaluate the association between telomere length and colorectal cancer risk using peripheral blood samples collected before cancer diagnosis. The study included 441 women with incident colorectal cancer and 549 matched controls. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. Multiple logistic regressions were used to derive adjusted OR with 95% confidence intervals (CI) as the measure of association between telomere length and subsequent colorectal cancer risk. RESULTS: A U-shaped association was observed between telomere length and colorectal cancer risk (test for nonlinearity P = 0.0112). Women with telomere length in the third quintile (40th-60th percentiles) had the lowest risk of colorectal cancer, and the risks were elevated with a shorter or longer telomere length. This U-shaped association did not statistically differ for colon cancer and rectum cancer. CONCLUSIONS AND IMPACT: Our prospective study revealed a U-shaped association between telomere length in peripheral blood cells and colorectal cancer risk. Our findings provide strong evidence that both very short and very long telomeres are associated with increased risk of colorectal cancer.