Androgen Receptor Gene and p21 Gene in Breast Cancer
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: Introduction: Androgens, which are usually thought of as male hormones, have many important functions in the female body. These functions are both indirect, through acting as a source of estrogen production, and direct, through binding to the androgen receptor (AR). Accumulating evidence has suggested that in female breast, these two modes of action might lead to different outcomes. The indirect effect contributes to increased breast cancer risk, while the direct effect may be protective. The overall effect will be the balance between these two. In our recently-completed study among women with and without breast cancer, we incorporated a genetic marker (AR variant) to specifically examine the direct effect of androgens. Our study found a relationship between the stronger AR variant and a reduced breast cancer risk among women whose mother or sister(s) had been affected by breast cancer, supporting the postulated protective direct effect of androgens. However, our previous study was very small and included only African-American women. Data are still too sparse to determine which groups of women might be protected by androgens. Therefore we propose to reexamine this question in two larger studies that include three racial groups. Moreover, we will explore possible mechanisms of the protective effect of androgens by examining one specific protein (p21) which plays a very important role in controlling the growth and division of normal and cancer cells. This protein was chosen for study because androgens can regulate its production.
 
 
 
 
 
 
 
 Hypotheses: We hypothesize that genetically-determined differences in the androgen action may predispose women to different risks of breast cancer, at least in some groups of women, for examples, women with relatives (mother or sisters) affected by breast cancer.
 
 
 
 
 
 
 
 Methodology: We will use DNA samples and other information collected from women with and without breast cancer in two studies conducted in Northern and Southern California. We will conduct genetic analyses on these DNA samples and later perform statistical analyses to determine whether women with genetically-determined high androgen action may have a lower risk of breast cancer.
 
 
 
 
 
 
 
 Innovative elements: The idea that androgens act directly as a protective factor in breast cancer is still very controversial. Data supporting this idea, although somewhat consistent, are very sparse. There is also a lack of well-conducted studies of the p21 protein in women with and without breast cancer. Our proposed study could provide new clues as to how androgens influence breast cancer risk in women.
 
 
 
 
 
 
 
 Advocacy involvement: Recently, there is a rapidly-growing interest in the use of androgen replacement in symptomatic women undergoing menopause. However recent news reports on the potential hazards of various types of hormone therapy (including androgens) raises great public concern about the possible use of androgens alone or in combination with estrogen and/or progeterone replacement therapy. Therefore it is critical to understand the functions of androgens in the breast, and how these functions might vary in different groups of women. If a direct protective effect of androgens can be demonstrated in some groups of women (such as those with a family history of breast cancer or those on postmenopausal hormone replacement therapy), then androgens might be useful for protecting these women from breast cancer.