Folate, Vitamin D and Calcium in Colorectal Cancer

叶酸、维生素 D 和钙在结直肠癌中的作用

• 批准号: 7616065
• 负责人: ROBERT William HAILE
• 金额: $ 42.98万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7616065
• 关键词: Address; Adenosylmethionine Decarboxylase; Alcohol dehydrogenase; Area; Calcium; Calcium-Sensing Receptors; Candidate Disease Gene; Chromosome Mapping; Colon; Colorectal Cancer; Commit; Cooperative Family Registry; DNA; Epidemiology; FOLR1 gene; Family; Folate; Funding; Genes; Genetic; Genotype; Genus Cola; Glycine Hydroxymethyltransferase; Haplotypes; Hydrolase; Hypermethylation; IBAT cotransporter; Institution; Interdisciplinary Study; Laboratories; MLH1 gene; MSH2 gene; MSH6 gene; Metabolism; Methionine; Mismatch Repair; Molecular; Mutation; Non-Steroidal Anti-Inflammatory Agents; Oxidoreductase; Pathway interactions; Publishing; RXR; Research; Research Infrastructure; Risk; SLC19A1 gene; Specimen; Stomach; TYMS gene; Testing; Thymidylate Synthase; Transcobalamin II; Transferase; Variant; Vitamin D; Vitamin D-Binding Protein; Vitamin D3 Receptor; adenosine deaminase; base; case control; folate-binding protein; folic acid metabolism; gene environment interaction; genetic epidemiology; interest; intrinsic factor-cobalamin receptor; methionine synthase reductase; receptor

DESCRIPTION (provided by applicant): The Cooperative Family Registry for Colorectal Cancer Studies (Colon CFR) is an NCI-supported consortium dedicated to the establishment of a comprehensive collaborative infrastructure for interdisciplinary studies in the genetics and genetic epidemiology of colorectal cancer. The cooperating institutions are collecting epidemiological information and laboratory specimens from families who represent the continuum of risk for colorectal cancer. A major area of etiological research to which the Colon CFR is committed is candidate gene association studies, where we plan to target selected "pathways", rather than focusing on isolated genes. This application, along with a parallel application submitted by Dr. John Potter, is meant to initiate the Colon CFR research on candidate genes. The Colon CFR has identified three pathways with which to start: folate metabolism and vitamin D/calcium, which are addressed in this application, and the NSAID pathway, which is addressed in Dr. Potter's application. For this application, we have the following specific aims: Folate. Conduct a family-based case-control association study of selected genes that are involved in the metabolism of folate. Our current list of genes of interest includes: serine hydroxymethyltransferase (SHMT1), mehylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), thymidylate synthase (TYMS or TS), S-adenosylhomocysteine hydrolase (AHCY or SAHH), ADA (adenosine deaminase), methionine adenosyl transferase 2A (MAT2A), folate receptor (FOLR1), reduced folate carrier (RFC1 or SLC19A1), S-adenosylmethionine decarboxylase (AMD1), gastric instrinsic factor (GIF), transcobalamin II (TCII), intrinsic factor cobalamin receptor (IFCR), and alcohol dehydrogenase 3 (ADH3). Vitamin D and Calcium. Conduct a family-based case-control association study of selected genes that are involved in the metabolism of vitamin D and calcium. Our current list of genes includes: vitamin D receptor (VDR), retinoid X receptor (RXR), vitamin D binding protein (DBF), calcium sensing receptor (CaSR), and the ileal sodium-dependent bile acid transporter (SLC10A2). Genotyping will primarily involve SNP-based haplotypes. For both pathways, analyses of gene-gene and gene-environment interactions will be included as appropriate.

描述（由申请人提供）：结直肠癌研究合作家庭登记处（Colon CFR）是一个由NCI支持的联盟，致力于为结直肠癌遗传学和遗传流行病学的跨学科研究建立全面的合作基础设施。各合作机构正在收集流行病学资料和来自具有结肠直肠癌连续风险的家庭的实验室标本。结肠CFR致力于病因学研究的一个主要领域是候选基因关联研究，我们计划靶向选定的“途径”，而不是专注于孤立的基因。该申请，沿着由John Potter博士提交的平行申请，旨在启动关于候选基因的Colon CFR研究。Colon CFR确定了三种起始途径：叶酸代谢和维生素D/钙，在本申请中讨论，以及NSAID途径，在Potter博士的申请中讨论。对于此应用程序，我们有以下具体目标：叶酸。对参与叶酸代谢的选定基因进行以家族为基础的病例对照关联研究。我们目前感兴趣的基因列表包括：丝氨酸羟甲基转移酶（SHMT 1）、亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合成酶（MTR）、甲硫氨酸合成酶还原酶（MTRR）、胸苷酸合成酶（TYMS或TS），S-腺苷高半胱氨酸水解酶（AHCY或SAHH）、ADA（腺苷脱氨酶）、甲硫氨酸腺苷转移酶2A（MAT 2A）、叶酸受体（FOLR 1）、还原型叶酸载体（RFC 1或SLC 19 A1）、S-腺苷甲硫氨酸脱羧酶（AMD 1）、胃内因子（GIF）、转钴胺素II（TCII）、内因子钴胺素受体（IFCR）和醇脱氢酶3（ADH 3）。维生素D和钙。对参与维生素D和钙代谢的选定基因进行以家族为基础的病例对照关联研究。我们目前的基因列表包括：维生素D受体（VDR），维甲酸X受体（RXR），维生素D结合蛋白（DBF），钙敏感受体（CaSR）和回肠钠依赖性胆汁酸转运蛋白（SLC 10A 2）。基因分型将主要涉及基于SNP的单倍型。对于这两种途径，将酌情包括基因-基因和基因-环境相互作用的分析。