Association of Telomere Length with Colorectal Cancer and Adenoma

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衰老和癌症风险的主要生物标志物。端粒是位于染色体末端的TTAGGG重复复合物，其保护染色体免于降解、融合和异常重组。由于端粒随着每个细胞复制周期而缩短，因此它们指示细胞所经历的分裂次数。较短的端粒长度与头颈癌、肺癌、肾细胞癌和膀胱癌、溃疡性结肠炎和结肠癌的风险相关;然而，尚未发表关于结肠直肠癌和腺瘤的前瞻性研究。我们建议在两项大型巢式病例对照研究（护士健康研究和卫生专业人员随访研究）中调查PBL中端粒长度与结直肠癌和腺瘤风险之间的关系。在样本的子集中，我们还将确定PBL中的端粒长度是否与配对的结直肠癌肿瘤样本中的端粒长度相关。此外，我们将研究端粒长度的环境和生活方式预测。我们对端粒长度的前瞻性测定不仅对于确认端粒长度作为风险标志物的价值特别重要，而且对于了解生活方式因素如何直接影响端粒缩短，可能导致降低结直肠癌和腺瘤风险的策略也特别重要。

DESCRIPTION (provided by applicant): 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.