Using Microarrays to Estimate Breast Cancer Risk
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Over the past decade, researchers have developed a better understanding of the characteristics (risk factors) that predispose certain women to breast cancer. Knowledge of these risk factors has led to methods, such as the Gail model, that can inform some women of their odds of developing breast cancer. The Gail model, while perhaps the most commonly used, has its limitations. Perhaps most importantly, less than half of the women who develop breast cancer would have been identified as high risk by the Gail method.
 
 
 
 
 
 
 
 Here, I propose to develop a new method of determining a woman's risk for breast cancer. My approach is based on the well-known link between exposure to x-rays and the subsequent development of breast cancer. For example, women who are exposed to high doses of x-rays as part of the treatment for Hodgkin's disease (a cancer of the immune system), have a markedly increased risk for breast cancer. In addition, all of the known breast cancer genes, including BRCA1 and BRCA2, normally function in the system that repairs damage from these x-rays.
 
 
 
 
 
 
 
 There are certainly other genes, or more likely combinations of genes, involved in both the repair of DNA damage from x-rays and the development of breast cancer. These genes can be identified using microarrays, a novel technology capable of analyzing the function of thousands of genes in a single experiment. I hypothesize that the development of breast cancer is intimately associated with an abnormal genetic response to exposure to x-rays, as detected on microarrays. This abnormal response can then be used to identify women at high risk of developing breast cancer.
 
 
 
 
 
 
 
 I will develop this method by performing a case-control study. I will identify and enroll a group of women with breast cancer (cases) as well as a similar group of women without breast cancer (controls). Each participant will donate a tube of their blood, and the blood cells will be grown in the laboratory. The cells from each patient will be exposed to x-rays in the lab, and the genetic response to the x-rays will be measured using a microarray. The responses from the women without breast cancer will be compared to those with breast cancer. A computer-based statistical method developed by my mentor will be used to identify the genes whose responses to x-rays predict the patients with breast cancer.
 
 
 
 
 
 
 
 This study represents a novel approach to the prediction and prevention of breast cancer. My strategy would allow breast cancer risk assessments to be tailored to each woman. It is based not on general risk factors applicable to many women, but instead on genetic factors that are specific to each individual. This method utilizes the powerful technology of microarrays, which was developed largely by colleagues of ours here at Stanford. When compared to other breast cancer risk assessment tools, our method should better identify high-risk women in the general population. The ability to identify women at elevated risk enables patients and their physicians to make highly educated choices among options for risk-reduction.