Circadian Genes and Breast Cancer

昼夜节律基因与乳腺癌

• 批准号: 6840724
• 负责人: YONG ZHU
• 金额: $ 8.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-03 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6840724
• 关键词: alcoholic beverage consumption; biomarker; breast neoplasms; cancer risk; carcinogenesis; circadian rhythms; disease /disorder etiology; female; gene environment interaction; genetic susceptibility; genotype; human data; human genetic material tag; human subject; molecular biology information system; neoplasm /cancer genetics; photobiology; single nucleotide polymorphism; smoking; tobacco abuse; women' s health

DESCRIPTION (provided by applicant): Emerging data have demonstrated that circadian genes are involved in regulating cell proliferation and apoptosis by controlling expression of tumor suppressor genes, cell cycle genes, as well as genes that encode the caspases and transcription factors. Therefore, as the molecular clockworks regulate many biological pathways in tumorigenesis, mutations in circadian genes could conceivably result in deregulation of these processes and tumour development. In this proposal, we hypothesize that adverse genotypes associated with these circadian genes may modulate their protein functions in biology rhythms, thereby influencing an individual's susceptibility to human cancer. Our specific aims are: 1) To identify single nucleotide polymorphisms (SNPs) with potential functional impact on circadian genes. SNPs will be collected from public SNP databases and screened by different bioinformatic tools. Prediction about functional impact will be made to both SNPs that alter an amino acid and SNPs located in the exonic splicing sites. 2) To determine the role that specific polymorphisms in these genes play in the modulation of breast cancer risk. Our hypothesis is that SNPs predicted to have functional significance in circadian genes may be a novel panel of biomarkers to be associated with breast cancer risk. 3) To investigate the joint-effect between circadian genes and environmental factors, especially night exposure to light. Light is the most powerful circadian synchronizer among all environmental cues. Our hypothesis is that exposure to light at night may disturb circadian rhythms and consequently increase the risk of breast cancer for individuals with the putative high-risk genotypes in circadian genes. Given the availability of DNA samples and exposure data, this proposal is both time and cost effective in terms of practical feasibility.

描述（由申请人提供）： 新兴数据表明，昼夜节律基因通过控制肿瘤抑制基因的表达，细胞周期基因以及编码caspase和转录因子的基因来调节细胞增殖和凋亡。因此，由于分子发条在肿瘤发生中调节了许多生物学途径，因此昼夜节律基因的突变可能会导致对这些过程和肿瘤发展的管制。在此提案中，我们假设与这些昼夜节律基因相关的不良基因型可能会调节其在生物学节奏中的蛋白质功能，从而影响个人对人类癌症的敏感性。我们的具体目的是：1）鉴定具有潜在功能影响昼夜节律基因的单核苷酸多态性（SNP）。 SNP将从公共SNP数据库中收集，并通过不同的生物信息学工具进行筛选。将对位于外显着剪接位点的氨基酸和SNP的两个SNP进行有关功能影响的预测。 2）确定这些基因在调节乳腺癌风险中发挥特定多态性的作用。我们的假设是，预测在昼夜节律基因中具有功能意义的SNP可能是与乳腺癌风险相关的新型生物标志物。 3）研究昼夜节律基因与环境因素之间的联合效应，尤其是夜间暴露于光。光是所有环境线索中最强大的昼夜节律同步器。我们的假设是，夜间暴露于光可能会干扰昼夜节律的节奏，从而增加昼夜节律基因假定高风险基因型的人患乳腺癌的风险。鉴于DNA样品的可用性和暴露数据，该建议在实际可行性方面既是时间又是成本效益。