Molecular Characterization of Sporadic Colorectal Cancer in the Young from India

印度年轻人散发性结直肠癌的分子特征

• 批准号: 7430672
• 负责人: JONATHAN R POLLACK
• 金额: $ 3.96万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7430672
• 关键词: Accounting; Adenomatous Polyposis Coli; Africa; Applications Grants; Asia; Asians; Award; Behavior; Cancer Etiology; Cancer Patient; Cancer cell line; Cessation of life; Cholangiocarcinoma; Class; Colon; Colorectal Cancer; Country; DNA Fingerprinting; DNA amplification; DNA copy number; Data; Data Analyses; Developed Countries; Developing Countries; Development; Diagnostic; Disease; Elderly; Europe; Future; Gene Amplification; Gene Deletion; Gene Expression; Gene Targeting; Genes; Genetic; Genome; Genomics; Genus Cola; Government; Head; Hereditary Malignant Neoplasm; Hereditary Nonpolyposis Colorectal Neoplasms; India; Inherited; International; International Union Against Cancer; Joints; Laboratories; Localized; Malignant Neoplasms; Malignant neoplasm of pancreas; Mentors; Microsatellite Instability; Mismatch Repair Gene Inactivation; Molecular; Molecular Profiling; Mutation; Numbers; Pancreas; Pathogenesis; Pathway interactions; Patients; Pattern; Personal Satisfaction; Predisposition; Protocols documentation; Public Health; Publishing; Rectum; Recurrence; Reporting; Research Personnel; Research Project Grants; Role; Sampling; Screening procedure; Signal Transduction; Standardization; Stress; Syndrome; Technology Transfer; Transcript; Tumor Biology; Tumor Suppressor Genes; Visit; WNT Signaling Pathway; Work; Xenograft procedure; anticancer research; base; beta catenin; cancer type; comparative; comparative genomic hybridization; design; experience; insight; molecular oncology; novel; older patient; pancreatic neoplasm; parent grant; transcriptomics; tumor; tumor initiation

DESCRIPTION (provided by applicant): The main aim of the proposed work is to understand the biology of tumors occurring in young sporadic colorectal cancer (CRC) patients. Colorectal cancer (CRC) is one of the most common lethal cancers in USA and Europe. Studies on CRCs have mainly focused on either older patients (above 50 years) or younger patients (below 50 years) with a familial predisposition. Two major forms of familial cancer syndromes have been well studied viz. the Hereditary Non-polyposis Colorectal Cancer (HNPCC) caused mainly due to germline inactivation of mismatch repair genes and the Familial Adenomatous Polyposis (FAP) caused mainly due to the germline inactivation of the Adenomatous Polyposis Coli tumor suppressor gene. Studies on sporadic CRCs occurring in the young have however been limited. Several recent reports have indicated an increase in the proportion of young sporadic CRC patients in developing countries in Africa and Asia, including India, as compared to USA and Europe. These patients account for almost 1/4th of the total CRC patients and often succumb to aggressive metastatic disease. Moreover, the tumor in these patients is usually localized to the rectum, as against similar young patients from the USA and Europe, in which case the tumor is predominantly localized to the colon. There are therefore several indications that suggest that the tumors occurring in the young may be distinct from similar tumors occurring in the elderly. In the present grant application, we propose a comprehensive comparative characterization of sporadic CRCs occurring in the young with those occurring in the elderly, from India. A multi-pronged strategy would be used including 1) screening for mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene, 2) determination of status of Wnt signaling through studies on beta-catenin and transcript profiling of Wnt target genes, 3) screening for microsatellite instability, 4) identification of recurrent DNA copy number alterations and 5) analyses of genome-wide gene expression profiles. The present study therefore is not only expected to yield valuable insights into the molecular basis for young sporadic CRC but may also provide inputs into cellular pathways governing tumor initiation and progression in general. Public Health Relevance: Colorectal cancer (CRC) is one of the most common and lethal cancers in the USA. Non-hereditary young CRC patients often are ill fated, and this type of cancer is not understood well. In our present study, we expect to define the detailed behavior of this class of tumors, which is expected to aid in designing more efficient therapies in the future.

描述（由申请人提供）：拟议工作的主要目的是了解年轻零星结直肠癌（CRC）患者中发生的肿瘤生物学。结直肠癌（CRC）是美国和欧洲最常见的致命癌症之一。关于CRC的研究主要集中于老年患者（超过50岁）或年轻患者（低于50岁），具有家族性倾向。两种主要形式的家族性癌症综合症已经很好地研究了。遗传性非型物结直肠癌（HNPCC）主要是由于种系失活了不匹配修复基因和家族性腺瘤性息肉病（FAP），这主要是由于腺瘤息肉病结肠癌抑制腺瘤性息肉抑制的种系造成的。然而，对年轻人发生的零星CRC的研究受到限制。最近的几份报告表明，与美国和欧洲相比，非洲和亚洲的发展中国家年轻的零星CRC患者比例增加了。这些患者占CRC总患者的近1/4，通常屈服于侵袭性转移性疾病。此外，与来自美国和欧洲的类似年轻患者相对，这些患者的肿瘤通常位于直肠，在这种情况下，肿瘤主要定位于结肠。因此，有几种迹象表明，在幼年中发生的肿瘤可能与老年人发生的类似肿瘤不同。在本赠款的申请中，我们提出了对年轻人发生的零星CRC的全面比较表征，来自印度的老年人。将使用多管齐下的策略，包括1）筛查腺瘤性息肉病（APC）抑制基因的突变，2）通过研究Wnta-catenin和Wnt靶基因的转录分析来确定Wnt信号的状态，3）3）筛选微观的不稳定性，4）复发性DNA拷贝数量的识别和5）范围分析范围和5）范围杂货数字，并浏览了5）。因此，本研究不仅被期望为年轻零星CRC的分子基础产生有价值的见解，而且还可以提供有关总体上肿瘤起始和进展的细胞途径的输入。公共卫生相关性：大肠癌（CRC）是美国最常见和致命的癌症之一。非遗传性的年轻CRC患者常常失败，这种类型的癌症对不太了解。在我们目前的研究中，我们希望定义这类肿瘤的详细行为，这有望将来设计更有效的疗法。