One-carbon nutrients in cancer prevention

一碳营养素预防癌症

基本信息

批准号：
7284838
负责人：
JOEL B MASON
金额：
$ 13.84万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7284838
关键词：
Address Affect Age Aging Animal Experiments Animals Award Biochemical Biological Biological Markers Carbon Cigarette Smoker Clinical Colon Colorectal Colorectal Cancer Complement DNA DNA Methylation DNA Microarray Chip DNA Microarray format DNA strand break Dose Elderly Epigenetic Process Equilibrium Folate Future Gene Expression Genes Genetic Genomics Genus Cola Human Individual Intake Laboratories Malignant Neoplasms Mediating Medical center Mentors Metabolism Methylation Microarray Analysis Modeling Molecular Mucous Membrane Nature Neoplasms Nutrient Oral cavity Pathway interactions Predisposition Principal Investigator Rattus Recording of previous events Research Design Research Personnel Research Proposals Resources Risk S-Phase Fraction Scientist Senior Scientist Award Smoking Supplementation Time Tobacco Training Uracil Vitamin B Complex Vitamin B Deficiency Vitamin B6 adenoma cancer prevention carcinogenesis career folic acid metabolism human study improved interest malignant mouth neoplasm novel nucleotide metabolism peripheral blood practical application response vitamin metabolism

项目摘要

DESCRIPTION (provided by applicant): Accumulating evidence from many different types of scientific studies indicate that inadequate intake of the B vitamin, folate, increases the risk of several cancers. The evidence is most compelling for cancer of the colorectum. However, the prevailing evidence suggests that folate depletion only results in cancer when it operates in concert with other ill-defined genetic and environmental predispositions to cancer. The principle investigator of this K05 application has devoted the majority of his career to investigating this relationship between folate and carcinogenesis. He is now poised to begin to investigate how several other factors, such as age, tobacco, and vitamin B6 and B12 depletion interact with folate metabolism in such a way as to accentuate the promotion of cancer conveyed by folate depletion alone. The financial resources afforded by this K05 award will enable the investigator to dispense with a very substantial burden of clinical and administrative duties in his medical center, thereby allowing him to devote nearly all of his professional energies towards the elucidation of the factors outlined above. The investigator also has an excellent track record of mentoring and has trained several young people who are now fully independent scientists themselves. This award, therefore, would free up enough of the Principal Investigator's time to enable him to take on additional trainees in the future. The studies that are intended to address the abovementioned issues include human and animal experiments that are complimentary in nature. Well-established rat models of B-vitamin depletion, aging, and colorectal carcinogenesis will be used to define which combinations of B-vitamin deficiencies and elder age can potentiate the procarcinogenic milieu produced by folate depletion, and by what mechanisms these effects are mediated. The identification of novel, previously unsuspected, pathways towards cancer will be elucidated by use of DNA microarray technology. A human study, designed to examine habitual cigarette smokers, will examine how smoking alters the metabolism of these vitamins in the mouth in order to convey an increased risk of oral cancer, and whether surrogate biomarkers of this cancer can be improved by the use of folate supplementation.

描述（由申请人提供）：从许多不同类型的科学研究中累积证据表明，叶酸B族维生素的摄入量不足会增加几种癌症的风险。证据最令人信服，对大肠癌的癌症。但是，普遍的证据表明，叶酸的耗竭仅在与其他不确定的遗传和环境易感性的癌症倾向时，才会导致癌症。该K05应用程序的主要研究者致力于他的大部分职业生涯，以调查叶酸与癌变之间的这种关系。现在，他准备开始研究其他几个因素，例如年龄，烟草和维生素B6和B12耗竭与叶酸代谢相互作用，以突出单独促进叶酸耗竭传达的癌症。该K05奖项提供的财政资源将使调查人员能够在其医疗中心承担非常重大的临床和行政职责负担，从而使他几乎将他的所有专业精力用于阐明上述因素。调查员还拥有指导的出色记录，并培训了几名年轻人，这些年轻人本身就是完全独立的科学家。因此，该奖项将释放足够的主要调查员的时间，使他将来能够接任其他学员。旨在解决上述问题的研究包括人类和动物实验本质上是免费的。 B-VITAMIN耗竭，衰老和结直肠癌发生的良好大鼠模型将用于定义哪种B-维生素缺乏症和老年年龄的组合可以增强叶酸消耗产生的procarcarcinic Milieu，以及通过这些效果介导的效果。通过使用DNA微阵列技术，将阐明新颖的癌症途径的新型癌症途径。一项旨在检查习惯吸烟者的人类研究将检查吸烟如何改变口腔中这些维生素的代谢，以传达口腔癌的风险增加，以及该癌症的替代生物标志物是否可以通过使用叶酸来改善补充。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Folic acid and vitamin B-12 supplementation does not favorably influence uracil incorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas.

补充叶酸和维生素 B-12 不会对既往患有结直肠腺瘤的受试者的直肠粘膜 DNA 中的尿嘧啶掺入和启动子甲基化产生有利影响。

DOI：
10.1093/jn/137.9.2114
发表时间：
2007
期刊：
The Journal of nutrition
影响因子：
0
作者：
vandenDonk,Maureen;Pellis,Linette;Crott,JimmyW;vanEngeland,Manon;Friederich,Pieter;Nagengast,FokkoM;vanBergeijk,JeroenD;deBoer,SybrandY;Mason,JoelB;Kok,FransJ;Keijer,Jaap;Kampman,Ellen
通讯作者：
Kampman,Ellen

Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.