Folate, Vitamin D and Calcium in Colorectal Cancer

描述（由申请人提供）：结肠直肠癌研究合作家庭登记处（Colon CFR）是一个nci支持的联盟，致力于建立一个全面的合作基础设施，用于结肠直肠癌遗传学和遗传流行病学的跨学科研究。合作机构正在从具有结直肠癌连续风险的家庭收集流行病学信息和实验室标本。结肠CFR致力于病原学研究的一个主要领域是候选基因关联研究，我们计划针对选定的“途径”，而不是专注于分离的基因。该申请连同约翰·波特博士提交的平行申请，旨在启动结肠CFR对候选基因的研究。结肠CFR已经确定了三种途径：叶酸代谢和维生素D/钙，这在本申请中得到了解决，以及非甾体抗炎药途径，这在波特博士的申请中得到了解决。对于这种应用，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基于家族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（SHMT1）、亚甲基四氢叶酸还原酶（MTHFR）、蛋氨酸合成酶（MTR）、蛋氨酸合成酶还原酶（MTRR）、胸苷酯合成酶（TYMS或TS）、s -腺苷同型半胱氨酸水解酶（AHCY或SAHH）、ADA（腺苷脱氨酶）、蛋氨酸腺苷转移酶2A （MAT2A）、叶酸受体（FOLR1）、还原性叶酸载体（RFC1或SLC19A1）、s -腺苷蛋氨酸脱羧酶（AMD1）、胃内源因子（GIF）、转钴胺素II （TCII）、内在因子钴胺素受体（IFCR）和酒精脱氢酶3 （ADH3）。维生素D和钙。对参与维生素D和钙代谢的选定基因进行基于家族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）、类维甲酸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（SLC10A2）。基因分型主要涉及基于snp的单倍型。对于这两种途径，基因-基因和基因-环境相互作用的分析将酌情包括在内。

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.