Telomere Length and Endometrial Cancer

描述(由申请人提供)： 在外周血白细胞(PBL)中测量的端粒长度已成为患癌症等慢性疾病风险的主要生物标志物。我们建议在两个大型嵌套病例对照研究中，即护士健康研究和妇女健康研究中，研究外周血淋巴细胞端粒长度与子宫内膜癌风险的关系。我们还希望确定端粒稳定性相关基因的多态是否影响子宫内膜癌的风险，例如编码端粒酶催化亚单位的hTERT。此外，我们希望评估环境和生活方式决定端粒长度的因素，这些因素可以被修改以降低子宫内膜癌的风险。子宫内膜癌主要由终生总暴露于游离雌激素决定，也是其他由激素决定的癌症的相关模型。因此，建立PBL中端粒长度与子宫内膜癌之间的关系将有助于更好地理解激素驱动的肿瘤形成的机制。我们对端粒长度的前瞻性测定对于确认端粒长度作为风险标记物的价值，以及了解生活方式因素如何直接影响端粒缩短，从而可能降低子宫内膜癌的风险都特别重要。

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.