4.4 Article

Association Between Leukocyte Telomere Length and Colorectal Cancer Risk in the Singapore Chinese Health Study

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.14309/ctg.0000000000000043

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Funding

  1. National Institutes of Health (NIH) of the United States [R01 CA144034, UM1 CA182876]
  2. National Medical Research Council, Singapore [NMRC/CSA/0055/2013]
  3. United States NIH Grant [1P20CA210300-01]
  4. University of Pittsburgh Medical Center Hillman Cancer Center start-up grant

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OBJECTIVES: Telomeres and telomerase play important roles in maintaining chromosome integrity and genomic stability. To address a lack of consensus about the association between leukocyte telomere length and colorectal cancer, we investigated this association in the Singapore Chinese Health Study. METHODS: Relative telomere length in white blood cells was quantified using a validated quantitative polymerase chain reaction method in 26,761 participants, including 776 incident colorectal cancer cases. The Cox proportional hazard regression method was used to calculate the hazard ratio and the corresponding 95% confidence interval (CI) for colorectal cancer associated with longer telomeres. RESULTS: Longer telomeres were significantly associated with a higher risk of colorectal cancer (P-trend = 0.02). Compared with the lowest quartile, subjects with the highest quartile of telomere length had a hazard ratio of 1.32 (95% CI: 1.08-1.62) for developing colorectal cancer. The corresponding elevation in rectal cancer risk for the highest quartile of telomere length was 71%(95% CI: 22-140, P-trend = 0.02). There was no statistically significant association between telomere length and risk of colon cancer. DISCUSSION: This large cohort study of Singapore Chinese, the first study using a cohort study design with more than 26,000 participants that yielded 776 incidence colorectal cancer cases during 12 years of follow-up, provides evidence in support of longer telomeres being associated with a higher risk of colorectal cancer, particularly rectal cancer.

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