Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis
Abstract
Risk factors for the development of breast cancer remain largely unknown, especially those associated with the effect of the environment. Despite the known influence of hormonal factors, breast tumorigenesis has been shown to involve an accumulation of serial genetic changes in cancer genes. X-irradiation is a genotoxic exposure that has been identified as a risk factor for breast cancer. If somatic mutation is a major mechanism that- drives the process of breast carcinogenesis, we hypothesize that breast cancer should develop preferentially in women with higher frequencies of somatic variation, as measured at a neutral reporter locus. The rate of somatic mutation is determined by exposure to endogenous and exogenous genotoxic agents and by an individual's ability to deal with such exposures through biotransformation of xenobiotics and DNA repair. We are using two established bioassays of in vivo human somatic mutation to study a large population of newly diagnosed primary breast cancer patients. These geneticlenvironmental interactions can be quantified simply from observed effect, before we have completely understood the underlying mechanisms. Our primary goal is to provide a rationale for simple laboratory blood tests to be incorporated into the risk estimation equation for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396384
Entities
People
- Stepen G. Grant
Organizations
- University of Pittsburgh