HER-2/neu Gene Variations and 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: There are important differences between breast cancers in African Americans and Whites. After taking tumor size, disease spread, and hormone-receptor status into consideration race remains as a factor effecting breast cancer survival. Our proposal is focused on understanding an important breast cancer-related gene (HER-2/neu) in normal cells from women with and without breast cancer. Approximately 25% of breast cancers duplicate the HER-2/neu gene repeatedly so they have multiple copies. This is referred to as HER-2/neu gene amplification. HER-2/neu gene amplification is associated with aggressive breast cancers and a shorter overall survival. By understanding the role of variants of the HER-2/neu gene in patients and healthy women we expect to gain understanding both of the role of this gene in breast cancer causation and in breast cancer prevention.
 
 
 
 
 
 
 
 While genes known to cause breast cancer, such as BRCA1 and BRCA2, are clearly important, few women have mutations in these genes. There is an emerging, possibly larger, role for "normal" gene variations, referred to as polymorphisms, which are wide-spread in the population but have weaker effects on the disease process. Racial differences in breast cancer may possibly be related to differences in the frequency of various "normal" genes (polymorphism) in these populations. 
 
 
 
 
 
 
 
 The HER-2/neu gene is one which can be present in either of two "normal" forms. One of these "normal" forms (a polymorphism) has been found to be associated with a higher risk of breast cancer in Chinese women. The role of this polymorphism in African American and white women has not been determined.
 
 
 
 
 
 
 
 We plan to investigate two "normal" forms of the HER-2/neu gene in a large number of African American and white women in Los Angeles County who participated in an epidemiologic case-control study. We will determine: 
 
 
 
 
 
 
 
 1. How frequent is the HER-2/neu polymorphism in African American and white women without breast cancer (control subjects)? 
 
 
 
 
 
 
 
 2. How frequent is the HER-2/neu polymorphism in African American and white women with breast cancer (cases)? 
 
 
 
 
 
 
 
 3. Does breast cancer risk vary according to whether a woman inherits the HER-2/neu olymorphism? 
 
 
 
 
 
 
 
 4. Is breast cancer risk higher or lower among women with the HER-2/neu polymorphism who have other exposures like early menses, late menopause, fewer or no pregnancies, never breast fed, used birth control pills, or hormone replacement therapy, or do not exercise? 
 
 
 
 
 
 
 
 5. Does inherited HER-2/neu polymorphism status effect which breast cancers have gene amplification? 
 
 
 
 
 
 
 
 The study will analyze blood cells from African American and white women with breast cancer (cases) and women without breast cancer (controls). The blood cell DNA will be characterized for an inherited "normal" polymorphism in the HER-2/neu gene. Breast cancer tissue will be analyzed for the acquired HER-2/neu gene change, HER-2/neu gene amplification. Information previously collected from these women will be compared with the laboratory results to determine if there are associations between various environmental exposures (especially hormonal exposure) and breast cancer risk. 
 
 
 
 
 
 
 
 This research should answer some new questions about breast cancer causation in African American and white women for a gene which known to play an important role in the disease process, in overall survival and in selection of breast cancer treatment. In addition, understanding the interaction of inherited HER-2/neu polymorphisms with breast cancer risk factors could be important in the prevention of breast cancer.