Grant Number:	1R03CA110937-01 Interpret this number
Primary Investigator:	Zhu, Yong
Organization:	Yale University
Project Title:	Circadian Genes and Breast Cancer
Fiscal Year:	2004

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.




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