Breast Cancer Susceptibility Genes in Very High Risk Women
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: A woman with relatives who have had breast cancer has a higher risk of developing the disease than a woman who does not have relatives with the disease. However, within identical twin pairs, the twin of a breast cancer case has an even higher risk of developing the disease than other women with a family history of breast cancer. We have developed a large twin registry and have identified nearly 1200 identical twin pairs in which one twin has had breast cancer and 276 pairs in which both twins have had breast cancer. Twins in the registry completed a questionnaire when they first volunteered to be part of the registry. We have studied the responses within pairs where both had breast cancer and we found that some well known risk factors for breast cancer, especially those related to earlier development and onset of menstruation, were strongly related to the twin who developed breast cancer first in the pair. Since these women are at a high genetic risk of disease, we want to test our hypothesis that genetic factors related to estrogen metabolism may occur more often in these pairs than in others where breast cancer is not as common.
 
 
 
 
 
 
 
 To test our hypothesis we need to obtain DNA from tissue blocks that were preserved when the breast cancer was first diagnosed and treated. In an earlier study we have begun to obtain these blocks and will complete the process with this study. In total, we will obtain tissue from 200 pairs of identical twins where both have breast cancer, 200 pairs where one has breast cancer, and 100 pairs in which neither have had breast cancer. We will compare the frequency of one genetic polymorphism (called the A2 allele on the CYP 17 gene) among these groups. This genetic polymorphism has been shown to be related to higher levels of estrogen in some women. We want to determine if this genetic factor occurs more often in the pairs where both have breast cancer than in the other pairs.
 
 
 
 
 
 
 
 This study is very important because not much is known about specific genetic factors related to breast cancer, other than the widely publicized BRCA1/2 genes. While those genes carry a high risk of developing breast cancer, they are not very common in the population and do not account for all of the cases who have reported having a family history of the disease. We know that young women with breast cancer are more likely to have a genetic factor related to the development of their disease; however, the actual number of cases caused by genetic factors is much greater among those diagnosed after menopause, because breast cancer is so much more common then. The genes responsible for this late disease are not known, but are more difficult to identify because only a small proportion of those with the gene get the cancer, presumably because other factors are required. The twins in this study represent a high genetic risk group and the estrogen related risk factors that we have seen are especially strong in the older twins. Thus the study can contribute important knowledge to identifying the additional genetic factors related to breast cancer.