Telomere Length and Endometrial Cancer

描述（由申请人提供）： 外周血白细胞（PBL）中测量的端粒长度已成为癌症等慢性疾病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 端粒长度与子宫内膜癌风险之间的关联。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（例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，可以修改这些因素以降低子宫内膜癌的风险。子宫内膜癌主要由终生接触游离雌激素的情况决定，并且是其他由激素决定的癌症的相关模型。因此，建立 PBL 端粒长度与子宫内膜癌之间的关系将有助于更好地了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尤其重要，既可以确认端粒长度作为风险标记的价值，也可以了解生活方式因素如何直接影响端粒缩短，从而可能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.