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慢性疾病如癌症风险的主要生物标志物。我们建议在两项大型巢式病例对照研究（护士健康研究和妇女健康研究）中调查PBL中端粒长度与子宫内膜癌风险之间的关系。我们还希望确定子宫内膜癌的风险是否受到端粒稳定性相关基因（如编码端粒酶催化亚基的hTERT）多态性的影响。此外，我们希望评估端粒长度的环境和生活方式决定因素，这些因素可以被修改以降低子宫内膜癌的风险。子宫内膜癌主要是由游离雌激素的终生暴露决定的，并且是其他子宫决定的癌症的相关模型。因此，建立外周血淋巴细胞端粒长度和子宫内膜癌之间的关系将提供一个更好的了解子宫内膜驱动的肿瘤的机制。我们对端粒长度的前瞻性测定将特别重要，既可以确认端粒长度作为风险标志物的价值，也可以了解生活方式因素如何直接影响端粒缩短，从而降低子宫内膜癌的风险。

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.