Estrogen Formation and Breast Cancer Risk

Institution: University of Southern California
Investigator(s): Gerhard Coetzee, Ph.D. -
Award Cycle: 1997 (Cycle III) Grant #: 3IB-0082 Award: $244,889
Award Type: IDEA
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle



Initial Award Abstract (1997)
The past 20 years of research have identified numerous risk and protective factors for breast cancer, many of which can be understood as being associated with differences in lifetime exposure to the female hormone, estrogen. In general, estrogen causes increased cell division in breast cells and this is thought to increase the chance of errors in the genetic material of some cells, resulting in cancer development.

Recently, two genes have been identified (called BRCA1 and 2), each one greatly enhancing the chance for breast cancer when any one of them carrying a mutation is inherited by a woman. However, it is estimated that only about 5% of all breast cancer in the U.S. is attributable to mutations in these two genes. We and others have proposed that several other genes might also contribute to breast cancer risk. Many such genes might each contribute only modestly to the risk of getting breast cancer. However, in the population at large, they might play important roles in combination due to their high prevalence. One such class of genes code for enzymes that control the formation of estrogen; the more active the enzyme, the more estrogen will be synthesized, the higher the risk is for breast cancer development. In this study we will focus on a candidate gene, called CYP17. This gene codes for the enzyme that specifically controls the ultimate formation of all estrogen in the body. Variant forms of this gene might be inherited by a woman. We have identified certain variant forms that might increase the risk for developing breast cancer, and this project will attempt to understand how these changes can cause differences in the enzyme’s activity and how these differences in turn might be related to risk of developing breast cancer.

We believe that the basic information forthcoming from this, and other studies like this, will lead to the better understanding of the known family associations of breast cancer. Such knowledge, combined with information of other genes, might ultimately lead to the rational formulation of risk assessment of breast cancer in the general population.


Final Report (1999)
The past 20 years of research have identified numerous risk and protective factors for breast cancer, many of which can be understood as being associated with differences in lifetime exposure to the female hormone, estrogen. In general, estrogen causes increased cell division in breast cells and this is thought to increase the chance of errors in the genetic material of some cells, resulting in cancer development. A class of genes code for enzymes and protein factors that control the formation and action of estrogen: the more active the enzyme or factor, the more estrogen action, and the higher the risk is for breast cancer development. In this study we focus on one such a candidate gene, called CYP17. This gene codes for the enzyme that specifically controls the ultimate formation of all estrogen in the body. So far we have identified several variant forms, some of which might increase estrogen production and thus the risk for developing breast cancer. We are in the process of establishing the assays to test the variant forms using cultured cells. We would like to understand how these genetic changes could cause differences in the enzyme's level of expression and activity and in turn how they might be related to risk of developing breast cancer. We believe that the basic information forthcoming from this, and other studies like this, will lead to the better understanding of the known family associations of breast cancer. Such knowledge, combined with information of other genes, might ultimately lead to the rational formulation of risk assessment of breast cancer in the general population at large.

Polymorphic exonic CAG microsatellites in the gene amplified in breast cancer
Periodical:Clinical Genetics
Index Medicus: Clin Genet
Authors: Shirazi SK, Bober MA, Coetzee GA
Yr: 1998 Vol: 54 Nbr: 1 Abs: Pg:102-3