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: 7405462
• 负责人: ROBERT William HAILE
• 金额: $ 42.56万
• 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 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7405462
• 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; FOLR1 gene; Family; Folate; Funding; Genes; Genetic; Genotype; Genus Cola; Glycine Hydroxymethyltransferase; Haplotypes; Hydrolase; Hypermethylation; IBAT cotransporter; Immunohistochemistry; Institution; Interdisciplinary Study; Laboratories; MLH1 gene; MSH2 gene; MSH6 gene; Metabolism; Methionine; Mismatch Repair; Molecular; Mutation; Non-Steroidal Anti-Inflammatory Agents; Oxidoreductase; Pathway interactions; Personal Satisfaction; Publishing; RXR; Research; Research Infrastructure; Risk; SLC19A1 gene; Specimen; Stomach; TYMS gene; Testing; Thymidylate Synthase; Today; 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(Colon CFR)是一个由NCI支持的联盟，致力于建立一个全面的协作基础设施，用于结直肠癌遗传学和遗传流行病学的跨学科研究。合作机构正在从代表结直肠癌风险连续统的家庭收集流行病学信息和实验室标本。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，我们计划以选定的“途径”为目标，而不是专注于孤立的基因。这项申请与约翰·波特博士提交的一份平行申请一起，意在启动对候选基因的科隆CFR研究。科隆CFR已经确定了三条开始的途径：本申请中涉及的叶酸代谢和维生素D/钙，以及波特博士的申请中涉及的非甾体抗炎药途径。对于这一应用，我们有以下具体目标：叶酸。对涉及叶酸新陈代谢的选定基因进行一项基于家庭的病例对照关联研究。我们目前感兴趣的基因包括：丝氨酸羟甲基转移酶(SHMT1)、四氢叶酸还原酶(MTHFR)、蛋氨酸合成酶(MTR)、蛋氨酸合成酶还原酶(MTRR)、胸苷合成酶(TYMS或TS)、S-腺苷同型半胱氨酸水解酶(AHCY或SAHH)、腺苷脱氨酶(ADA)、蛋氨酸腺苷转移酶2A(MAT2A)、叶酸受体(FOLR1)、还原叶酸载体(RFC1或SLC19A1)、S-腺苷蛋氨酸脱羧酶(AMD1)、内源性因子(GIF)、转钴胺II(TCII)、内在因子钴胺受体(IFCR)和酒精脱氢酶3(H3)。维生素D和钙。对涉及维生素D和钙代谢的选定基因进行一项基于家庭的病例对照关联研究。我们目前的基因清单包括：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)和回肠钠依赖胆汁酸转运蛋白(SLC10A2)。基因分型将主要涉及基于SNP的单倍型。对于这两条途径，将酌情包括对基因-基因和基因-环境相互作用的分析。