Validation of Metabolic Signature Epigenetic Biomarkers for Colon Cancer Risk

结肠癌风险代谢特征表观遗传生物标志物的验证

基本信息

批准号：
8692719
负责人：
CARMEN SAPIENZA
金额：
$ 7.57万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8692719
关键词：
Accounting Affect Age Aging Asthma Biochemical Biological Markers Blinded Cancer Control Cancer Etiology Cancer Patient Candidate Disease Gene Carbohydrates Cessation of life Clinical Collection Colon Colon Carcinoma Colonic Neoplasms Colonic Polyps Colonoscopy DNA Methylation Data Development Diagnosis Diagnostic Diagnostic tests Diet Dietary Component Dietary Factors Disease Disease Progression Environmental Exposure Epigenetic Process Event Fossils Genes Genetic Genetic Risk Human Human Genome Incidence Individual Inherited Link Logistic Regressions Malignant Neoplasms Measures Medical Metabolic Methods Methylation Molecular Mucous Membrane Mutation Non-Insulin-Dependent Diabetes Mellitus Pathway interactions Patients Population Population Control Predictive Value Predisposition Prognostic Marker Publishing Receiver Operator Characteristics Recording of previous events Relative Risks Risk Role Sampling Site Testing Transcript United States Validation Variant Veins Woman cancer diagnosis cancer risk carbohydrate metabolism cigarette smoking efficacy testing epigenetic marker genome sequencing human disease improved insulin signaling interest lipid metabolism men outcome forecast public health relevance research study screening success tool tumor progression

项目摘要

DESCRIPTION (provided by applicant): One of the long-awaited promises of the human genome sequencing project is the identification of genes involved in common human disease. Human geneticists have identified genes involved in type 2 diabetes, asthma, and many other common diseases. Despite these successes, there has been little translational impact of identifying these "common disease genes" because the relative risk of developing disease for carriers of each defective gene is small. Although this fact is not surprising to geneticists, it bgs the question of what type of information could be added to genetic risk data to increase the predictive power of who is at highest or lowest risk for any particular disease. In this vein, ther is great interest in the potential for "epigenetic markers" to add predictive value to genetic risk data. There is perhaps no better case for a major role for epigenetic effects in common disease than colon cancer. Colon cancer accounts for more than 10% of all invasive cancer cases in the United States and more than 100,000 new cases are diagnosed each year. It is the third most common cancer in both men and women and the third leading cause of cancer deaths. Epigenetic alterations are associated with both increased risk of disease and tumor progression. Moreover, there is compelling evidence linking environmental influences such as western diets and cigarette smoking with increased risk of colon cancer. Our hypothesis is that systemic epigenetic differences and environmentally-induced epigenetic changes are associated with increased risk of colon cancer and that these differences can be distinguished in colon mucosa that appears otherwise "normal". We published the results of a pilot experiment that compared the normal colon mucosa of cancer patients with the normal colon mucosa of individuals who did not have cancer or colon polyps and found highly significant differences in DNA methylation at many of the genes involved in the metabolism of lipids and carbohydrates (dietary components that may be involved in increased risk of colon cancer), as well as insulin signaling. In this project, we propose to validate a set of these DNA methylation differences that are likely to result from dietary factors in cancer-prone individuals. If validated in an independent group of patients, this set of DNA methylation differences will constitute an epigenetic metabolic signature of colon cancer risk. A collection of such biomarkers would constitute a quantitative, clinically useful biochemical tool to assess cancer risk.

描述（由申请人提供）：人类基因组测序项目的期待已久的承诺之一是鉴定了与普通人类疾病有关的基因。人类遗传学家已经确定了与2型糖尿病，哮喘和许多其他常见疾病有关的基因。尽管取得了这些成功，但识别这些“常见疾病基因”的翻译影响很小，因为每个有缺陷基因的携带者的相对风险很小。尽管这一事实对遗传学家来说并不奇怪，但它bgs的问题是，可以将哪种类型的信息添加到遗传风险数据中，以提高谁对任何特定疾病的风险最高或最低风险的预测能力。在这种情况下，这对“表观遗传标记”的潜力非常感兴趣，以增加遗传风险的预测价值数据。也许没有比结肠癌更好的表观遗传作用的主要作用。在美国，结肠癌占所有侵入性癌症病例的10％以上，每年诊断出100,000多例新病例。它是男性和女性中第三大常见的癌症，也是癌症死亡的第三主要原因。表观遗传改变与疾病风险增加和肿瘤进展有关。此外，还有令人信服的证据将环境影响（例如西方饮食和吸烟与结肠癌风险增加）联系起来。我们的假设是，全身表观遗传学差异和环境诱发的表观遗传变化与结肠癌的风险增加有关，并且在结肠粘膜中可以区分这些差异，这些差异似乎是正常的。我们发表了一项试验实验的结果，该实验比较了癌症患者的正常结肠粘膜与没有癌症或结肠息肉的个体正常结肠粘膜，发现在脂质和碳水化合物的代谢中涉及的许多基因的DNA甲基化在DNA甲基化方面存在很大显着差异（饮食成分的饮食成分（饮食成分）可能会增加Colon color coll Carly collist Carlon and Color Chorce）。在这个项目中，我们建议验证一组这些DNA甲基化差异，这些甲基化差异可能是由于容易发生癌症的个体而导致的。如果在一个独立组中进行了验证患者，这组DNA甲基化差异将构成结肠癌风险的表观遗传代谢特征。此类生物标志物的集合将构成一种定量，临床上有用的生化工具，以评估癌症风险。