Telomere Length and Endometrial Cancer

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DESCRIPTION (provided by applicant): Telomere length measured in peripheral blood leucocytes (PBLs) has emerged as a principal biomarker for risk of chronic diseases such as cancer. We propose to investigate the association between telomere length in PBLs and risk of endometrial cancer in two large nested case-control studies, the Nurses' Health Study and the Women's Health Study. We also wish to determine whether the risk of endometrial cancer is influenced by polymorphisms in telomere-stability related genes such as hTERT that encodes the catalytic subunit of telomerase. Additionally, we wish to assess environmental and lifestyle determinants of telomere length that can be modified to reduce risk of endometrial cancer. Endometrial cancer is primarily determined by total lifetime exposure to free- estrogens and is a pertinent model for other hormonally determined cancer. Therefore, establishing a relationship between telomere length in PBLs and endometrial cancer would provide a greater understanding of the mechanisms involved in the hormonally driven neoplasia. Our prospective determination of telomere length would be particularly important, both for confirming the value of telomere length as a risk marker, as well as for understanding how lifestyle factors directly impact telomere shortening, and thus might reduce risk of endometrial cancer.