Psychosocial Stress, Glucocorticoid Signaling, and Prostate Cancer Health Disparities in African American Men.

Recent advances in our understanding of racial disparities in prostate cancer (PCa) incidence and mortality that disproportionately affect African American (AA) men have provided important insights into the psychosocial, socioeconomic, environmental, and molecular contributors. There is, however, limited mechanistic knowledge of how the interplay between these determinants influences prostate tumor aggressiveness in AA men and other men of African ancestry. Growing evidence indicates that chronic psychosocial stress in AA populations leads to sustained glucocorticoid signaling through the glucocorticoid receptor (GR), with negative physiological and pathological consequences. Compelling evidence indicates that treatment of castration-resistant prostate cancer (CRPC) with anti-androgen therapy activates GR signaling. This enhanced GR signaling bypasses androgen receptor (AR) signaling and transcriptionally activates both AR-target genes and GR-target genes, resulting in increased prostate tumor resistance to anti-androgen therapy, chemotherapy, and radiotherapy. Given its enhanced signaling in AA men, GR-together with specific genetic drivers-may promote CRPC progression and exacerbate tumor aggressiveness in this population, potentially contributing to PCa mortality disparities. Ongoing and future CRPC clinical trials that combine standard of care therapies with GR modulators should assess racial differences in therapy response and clinical outcomes in order to improve PCa health disparities that continue to exist for AA men.

Glucocorticoids Induce Stress Oncoproteins Associated with Therapy-Resistance in African American and European American Prostate Cancer Cells.

Glucocorticoid receptor (GR) is emerging as a key driver of prostate cancer (PCa) progression and therapy resistance in the absence of androgen receptor (AR) signaling. Acting as a bypass mechanism, GR activates AR-regulated genes, although GR-target genes contributing to PCa therapy resistance remain to be identified. Emerging evidence also shows that African American (AA) men, who disproportionately develop aggressive PCa, have hypersensitive GR signaling linked to cumulative stressful life events. Using racially diverse PCa cell lines (MDA-PCa-2b, 22Rv1, PC3, and DU145) we examined the effects of glucocorticoids on the expression of two stress oncoproteins associated with PCa therapy resistance, Clusterin (CLU) and Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75). We observed that glucocorticoids upregulated LEDGF/p75 and CLU in PCa cells. Blockade of GR activation abolished this upregulation. We also detected increased GR transcript expression in AA PCa tissues, compared to European American (EA) tissues, using Oncomine microarray datasets. These results demonstrate that glucocorticoids upregulate the therapy resistance-associated oncoproteins LEDGF/p75 and CLU, and suggest that this effect may be enhanced in AA PCa. This study provides an initial framework for understanding the contribution of glucocorticoid signaling to PCa health disparities.

Physician Consultations, Prostate Cancer Knowledge, and PSA Screening of African American Men in the Era of Shared Decision-Making.

African American (AA)/Black men are more likely to develop aggressive prostate cancer (PCa), yet less likely to be screened despite guidelines espousing shared decision-making regarding PCa screening and prostate-specific antigen (PSA) testing. Given the documented racial disparities in PCa incidence and mortality, engaging interactions with physicians are especially important for AA/Black men. Thus, this study evaluated occurrence of physician-patient conversations among AA/Black men, and whether such conversations were associated with PCa knowledge. We also quantified the serum PSA values of participants who had, and had not, discussed testing with their physicians. Self-identified AA/Black men living in California and New York, ages 21-85, donated blood and completed a comprehensive sociodemographic and health survey ( n = 414). Less than half (45.2%) of participants had discussed PCa screening with their physicians. Multivariate analyses were used to assess whether physician-patient conversations predicted PCa knowledge after adjusting for key sociodemographic/economic and health-care variables. Increased PCa knowledge was correlated with younger age, higher income and education, and having discussed the pros and cons of PCa testing with a physician. Serum PSA values were measured by ELISA. Higher-than-normal PSA values were found in 38.5% of men who had discussed PCa screening with a physician and 29.1% who had not discussed PCa screening. Our results suggest that physician-AA/Black patient conversations regarding PCa risk need improvement. Encouraging more effective communication between physicians and AA/Black men concerning PCa screening and PSA testing has the potential to reduce PCa health disparities.

Prostate Cancer Screening among High-Risk Black Men.

We explored potential barriers and facilitators for prostate cancer screening choices among high-risk Black men. In our sample of 264 Black men over 45 years of age living in the U.S. who met the American Cancer Society criteria for screening, we found that only 49.6% had ever been screened. We investigated potential barriers including screening intention, access to care, medical mistrust, and fatalism. Potential facilitating factors investigated were provider-patient conversations encompassing the pros and cons of screening, ethnicity taken into account, insurance, and previous prostate cancer screening. Recommendations and resources are suggested to increase screening of high-risk Black men.

Geographic patterns of change over time in mammography: Differences between Black and White U.S. Medicare enrollees.

U.S. Black women have higher breast cancer mortality compared to White women while their rate of ever having a mammogram has become equal to or slightly surpassed that of Whites. We mapped the distribution of change in screening mammography for Black and White female Medicare enrollees ages 67-69 from 2008 to 2012 by hospital referral region across the contiguous U.S., performed cluster analysis to assess spatial autocorrelation, and examined the screening differences between these groups in 2008 and 2012 respectively. Changes in screening mammography are not consistent across the U.S.: Black and White women have increased and decreased their use of mammography in different regions and Black women's change patterns vary more widely.

A review of hair product use on breast cancer risk in African American women.

The incidence rate of breast cancer for African American women has recently converged with that of non-Hispanic White women in the United States, although African Americans have a higher mortality rate due to this disease. Although most research exploring health disparities associated with this phenomenon has focused on differences between women based on biology and behavior, both the academic and lay communities have begun to explore the potential role of environmental exposure to estrogen and endocrine disrupting chemicals (EDCs). This study reviews the current state of the science associating one such means of exposure, hair products containing EDCs, with breast cancer risk in African American women. We found a growing body of evidence linking: (1) environmental estrogen and EDC exposures to breast cancer risk, (2) the presence of such chemicals in personal care products, including hair products, and (3) the use of certain hair products with potential breast cancer risk in African Americans. At the same time, there is also increasing concern in the lay community about this risk. These results indicate the need for additional research, and the opportunity to benefit from strategic partnerships in community-collaborative approaches in order to better understand the potential "cost of beauty."