One-carbon nutrients in cancer prevention

描述(由申请人提供)：从许多不同类型的科学研究中积累的证据表明，维生素B，叶酸的摄入不足，会增加患几种癌症的风险。对于结直肠癌来说，证据是最令人信服的。然而，普遍的证据表明，叶酸枯竭只有在与其他定义不清的遗传和环境易患癌症的因素协同作用时才会导致癌症。 这位K05应用的首席调查员将他职业生涯的大部分时间都投入到研究叶酸与癌症发生之间的关系上。他现在准备开始研究其他几个因素，如年龄、烟草和维生素B6和B12的枯竭如何与叶酸代谢相互作用，从而强调单独叶酸枯竭所传递的癌症促进作用。K05奖所提供的财政资源将使研究人员能够免除其医疗中心非常沉重的临床和行政职责负担，从而使他能够将几乎所有的专业精力投入到上述因素的阐明中。这位研究人员在指导方面也有很好的记录，并培训了几名年轻人，他们现在自己也是完全独立的科学家。因此，这项奖励将为首席调查员腾出足够的时间，使他能够在未来聘请更多的受训人员。 旨在解决上述问题的研究包括人类和动物实验，这些实验在性质上是互补的。已建立的B族维生素缺乏、衰老和结直肠癌的大鼠模型将被用来确定B族维生素缺乏和老年的哪种组合可以加强叶酸缺乏所产生的癌前环境，以及这些影响是通过什么机制介导的。通过使用DNA微阵列技术，将阐明新的、以前从未被怀疑的致癌途径。一项旨在检查习惯吸烟的人的研究将研究吸烟如何改变这些维生素在口腔中的新陈代谢，从而增加患口腔癌的风险，以及使用叶酸补充剂是否可以改善这种癌症的替代生物标志物。

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.