Telomere length measured in peripheral blood leucocytes (PBLs) has emerged as a principal biomarker of aging and cancer risk. Telomeres are TTAGGG repeat complexes at the end of chromosomes that protect against degradation, fusion, and aberrant recombination of chromosomes. As telomeres shorten with each cell replication cycle, they indicate the number of divisions a cell has undergone. Shorter telomere length has been associated with risks of head and neck, lung, renal cell and bladder cancers, ulcerative colitis and colon cancer;however, no prospective studies of colorectal cancer and adenoma have been published. We propose to investigate the association between telomere length in PBLs and risk of colorectal cancer and adenoma in two large nested case-control studies, the Nurses'Health Study and the Health Professionals Follow-Up Study. In a subset of the samples, we will also determine whether telomere length in PBLs is correlated with telomere length in paired colorectal cancer tumor samples. In addition, we will examine the environmental and lifestyle predictors of telomere length. Our prospective determination of telomere length will be particularly important not only for confirming the value of telomere length as a risk marker, but also for understanding how lifestyle factors directly affect telomere shortening, possibly leading to strategies to reduce risk of colorectal cancer and adenoma.
Considering how telomere length might influence colorectal cancer and adenoma development opens a new avenue of colorectal neoplasia research. Our prospective determination of telomere length will be particularly important not only for confirming the value of telomere length as a risk marker, but also for understanding how lifestyle factors directly affect telomere shortening, possibly leading to strategies to reduce risk of colorectal cancer and adenoma. This research will contribute to the scientific basis for identifying high-risk individuals for colorectal neoplasia and providing individualized risk management strategies. Public Health Significance This application will evaluate a possible role for peripheral blood leukocyte telomere length, as an easily-measured and non-invasive biomarker, for identifying individuals with high risk of sporadic colorectal neoplasia. Understanding the role of telomere shortening and how lifestyle factors directly affect telomere shortening, may lead to strategies to reduce risk of colorectal cancer and adenoma.
