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Introduction/Purpose: Black women now have higher breast cancer (BC) incidence and mortality than White women. They also use more hair products containing hormonally-active chemicals. Studies are beginning to link chemical ingredients in these products to BC risk. Little is known about community knowledge of BC and the potential association with hair product-related risk. The purpose of this study was to evaluate the hazard level of hair products used by Black women, and assess their knowledge about BC and hair product-related risks. Methodology: We employed principles of community-based participatory research and conducted the study through partnership between community advocates and university scientists. We collected hair products from locations frequented by Black women and hair stylists and used the Environmental Working Group's Skindeep© database to evaluate ingredient toxicity. We then explored knowledge of BC and hair product-related risk using a 41-item survey. Survey data were analyzed using SPSS. Results: All 54 products evaluated contained hazardous ingredients. Fourteen of the ingredients had an overall high hazard rating between 7-10, with 10 indicating very high levels of toxicity. The potential harmful effects of these chemicals include cancer, endocrine disruption and reproductive system toxicant. Survey data showed most women (62%) in the sample had a college or graduate degree. Participants (n=211) were more knowledgeable about the diagnosis and treatment of BC (46.3%), lifestyle-related risk factors (59.6%), and genetic risk factors (54.9%) than about hair product risk (40.8%). Conclusion: Several hair products frequently used by black women contained ingredients that have potential links to BC. Though the women in this study were highly educated, they had limited knowledge about the association between BC and toxins found in hair products. Research should further clarify the link between hair products and BC risk. As knowledge is evolving, given our emerging risk understanding, health educators and community advocates can promote efforts for women to learn more about exposure reduction to help them make informed decisions about the risk beauty product chemicals may hold regarding cancer. There is also a need for policies on personal care products that aim to protect the health of our communities. Citation Format: Dede Teteh, Phyllis Clark, Lenna Dawkins-Moultin, Rick Kittles, Susanne Montgomery. My crown or my health: Black women's knowledge of breast cancer and hair product-related risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5290.

Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of cancer-related deaths in American men. African American (AA) men are more likely to be diagnosed with aggressive PCa at a younger age and twice as likely to die from the disease as European American (EA) men. In order to reduce PCa mortality and its associated racial disparities, there is a critical need to identify and target pathways responsible for PCa aggressiveness. An unexplored target is the plasminogen system, which is key to cancer cell migration and tissue invasion during metastasis. During inflammation, activation of the plasminogen pathway degrades extracellular fibrin networks; however, in the context of cancer, this activation promotes cancer tissue invasion and metastasis. Mounting evidence shows that the glycolytic enzyme alpha-enolase (ENO1) plays a vital role in both increased energy metabolism and plasminogen activation during cancer progression and metastasis. Using immunoseroproteomic profiling of anti-tumor autoantibody responses in AA and EA men with PCa, we identified several tumor-associated autoantigens with functions in glycolysis and plasminogen signaling, including ENO1, annexin A2, fructose bisphosphate aldolase, glucose-regulated protein 78, glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. In a cohort of PCa (N=157) and non-PCa sera (N=183), we found a significantly higher frequency of autoantibodies to ENO1 in patients with PCa (p Citation Format: Tino Wilson Sanchez, Guangyu Zhang, Jitian Li, Liping Dai, Saied Mirshahidi, Nathan R. Wall, Clayton Yates, Colwick Wilson, Susanne Montgomery, Jian-Ying Zhang, Carlos A. Casiano. Targeting the tumor-associated autoantigen alpha-enolase in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1130. doi:10.1158/1538-7445.AM2017-1130

Prostate cancer (PCa) presents the greatest US cancer health disparity in terms of incidence and mortality, disproportionately affecting African American (AA) men. The biological characteristics of prostate tumors are exaggerated in AA men compared to European American (EA) men at time of diagnosis. The mechanisms underlying increased PCa aggressiveness in AA men are not fully understood; therefore, there is a critical need to identify biological determinants contributing to PCa mortality disparities. Glucocorticoids—a type of stress hormone—have been implicated as driving factors in PCa progression. The underlying mechanism involves endogenous glucocorticoid (cortisol) binding to its glucocorticoid receptor (GR) and activating genes that promote tumor aggressiveness and therapy resistance. A clinical dilemma exists as glucocorticoids, important in the palliative care of PCa patients, are now emerging as accelerators of disease progression and shortened survival. Chronically elevated levels of cortisol have been documented in AA men compared to EA men. This unhealthy cortisol production has been linked to stressful life events, which occur more frequently in the AA population. In addition, AA men are more sensitive to glucocorticoid exposure than EA men. These observations support the hypothesis that chronic stress leading to elevated cortisol in AA men may contribute to PCa health disparities. This study focused on examining the effects of glucocorticoid agonists and antagonists on the expression of stress oncoproteins, particularly LEDGF/p75 (Lens epithelial-derived growth factor of 75 kd) and CLU (clusterin), which are upregulated in PCa tumors and promote features of tumor aggressiveness, including resistance to clinically relevant taxanes used for advanced PCa treatment. We exposed a racially diverse panel of PCa cell lines, MDA-PCa-2b, 22Rv1, PC3, and DU145, to glucocorticoids (cortisol and dexamethasone), and observed by immunoblotting a time and dose-dependent upregulation of GR, LEDGF/p75 and CLU, particularly and more robustly in AA cells. Treatment of cells with mifepristone, a GR antagonist, attenuated this glucocorticoid-induced upregulation. In addition, siRNA- and shRNA-knockdown of LEDGF/p75 in PC3 cells resulted in decreased GR expression, suggesting a functional interplay between these two proteins in PCa cells. Interestingly, we also observed, using ELISA, increased circulation levels of LEDGF/p75 in AA PCa patients compared to EA patients and non-PCa controls, suggesting that this stress oncoprotein might play a more prominent role in AA PCa patients. These findings imply that activation of GR-signaling by glucocorticoids contributes to the activation of stress survival pathways associated with PCa aggressiveness and chemoresistance. These results add to the emerging contribution of GR signaling in PCa, particularly in the context of PCa health disparities. Citation Format: Leanne Woods-Burnham, Arthur Love, Christina K. Cajigas-Du Ross, Laura Stiel, Evelyn S. Sanchez, Kwame Amponsah, Susanne Montgomery, Colwick Wilson, Carlos A. Casiano. Glucocorticoid-mediated upregulation of stress oncoproteins: implications for prostate cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5285. doi:10.1158/1538-7445.AM2017-5285

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. This cancer is more aggressive in African American (AA) men, who are twice as likely to die from the disease when compared to other racial groups. Despite these racial disparities in PCa mortality, studies on PCa biology and biomarker discovery include mostly patients from European American (EA) backgrounds. There is a critical need to find minimally invasive PCa biomarkers that could aid in diagnosis and prognosis, especially in high risk populations like AA men. Immunoproteomics offers a minimally invasive approach to detect early malignant processes that trigger production of autoantibodies to tumor-associated antigens (TAA). We used serum samples from AA (n = 59) and EA (n = 50) men with PCa to probe one- and two-dimensional Western blots of protein lysates from aggressive PCa cell lines. AA PCa patient sera showed stronger immunoreactivity to proteins in PC3 cell lysates compared to the EA sera, with a 50 kD protein band frequently targeted by autoantibodies in several AA PCa sera. Serological proteomic analysis with mass spectrometry showed that these AA PCa autoantibodies recognized alpha-enolase (ENO1), a protein important in tumor formation, expansion, and glucose metabolism. In addition, several other glycolytic enzymes important for tumor proliferation were also identified as candidate prostate TAA, including GAPDH, bisphosphate aldolase, phosphoglycerate kinase, and lactate dehydrogenase. The ENO1 autoantibody frequency, measured by ELISA in sera from 400 racially diverse men with and without PCa, was four-fold higher in PCa compared to non-PCa patients. Interestingly, although sera from AA men with PCa had stronger WB reactivity to ENO1 present in PC3 lysates compared to EA men, and the ENO1 autoantibodies were initially discovered in eight AA PCa sera but only in two EA sera, the anti-ENO1 autoantibody frequency measured by ELISA, which used yeast-purified recombinant human ENO1 as a substrate, was higher in the EA PCa cohort. In addition, several anti-ENO1 positive sera from AA men with PCa showed increased immunoreactivity to this protein in the PCa cell lines LNCaP, MDA-PC2b, PC3, and DU145, but not against the purified ENO1 used in ELISA. The opposite was true in the EA PCa cohort, where strong reactivity against the purified ENO1 did not correlate with an equally strong immunoreactivity against the cellular ENO1. The EA PCa sera did not recognize the pattern of ENO1 expression observed with the AA sera in the same panel of prostate cell lines. These differences of immunoreactivity between AA and EA sera against PC3-ENO1 vs recombinant human ENO1 suggest that select AA sera may predominantly recognize ENO1 epitopes not displayed in the purified protein. These discrepancies point to racial differences in the immune response to prostate tumors. Citation Format: Tino Wilson Sanchez, Jian-Ying Zhang, Liping Dai, Susanne Montgomery, Colwick Wilson, Guangyu Zhang, Saied Mirshahidi, Nathan Wall, Carlos A. Casiano. Immunoproteomic profiling in African American men with prostate cancer: Evidence for an autoimmune response to glycolytic enzymes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3895.

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. PCa is diagnosed more frequently in African American men (AA), with a mortality rate that is two-fold higher than in other ethnic groups. The current diagnostic test for PCa relies on the detection of prostate specific antigen (PSA). Although this minimally invasive test has high sensitivity, its limited specificity leads to false positives and unnecessary biopsies. This test may also fail to recognize PCa in men with low PSA levels, especially in obese and young AA men. Therefore, there is a critical need for identifying additional minimally invasive PCa biomarkers, especially in high-risk populations such as AA men. Immunoseroproteomics is a powerful approach for profiling circulating autoantibodies targeting tumor-associated antigens (TAAs) in cancer patients. These autoantibodies may serve as “reporters” to tumorigenic events and potential diagnostic biomarkers relevant to tumor biology. Based on recent reports of racial differences in the immunobiology of PCa, we hypothesized that AA and CC men with PCa may produce different anti-TAA autoantibody profiles. To evaluate this hypothesis, total proteins from aggressive PCa cells were separated by one or two-dimensional (2D) gel electrophoresis and then probed by immunoblotting with sera from AA (n = 40) and CC (n = 50) PCa patients to identify immunoreactive protein bands or spots. Protein spots recognized by the patient sera were then excised from the 2D gels and analyzed by mass spectrometry to profile the anti-TAA autoantibody repertoire in a given patient. Sera from AA PCa patients showed stronger immunoreactivity against PC3 cell proteins than sera from the CC cohort when evaluated under identical conditions in immunoblots. A common immunoreactive band around 45-50kD was produced by several AA sera (n = 8), and by one CC serum, and subsequent analysis by mass spectrometry showed that it corresponded to alpha-enolase. Confirmation that the AA PCa sera recognized 47kD alpha-enolase was obtained by immunoblots showing that these sera recognized the same protein bands recognized by a monoclonal antibody to this protein. Some of these sera also reacted against annexin A2. Additional validation studies are currently under way. Alpha-enolase and annexin A2 have been recently identified as candidate plasminogen receptors with roles in PCa. Alpha-enolase has been shown to promote cancer aggressiveness properties and its expression in tumors is associated with poor clinical outcomes. Alpha-enolase is a promising candidate biomarker that if used in combination with other TAAs for autoantibody profiling in PCa might help in the early detection and management of PCa, particularly in AA men. Citation Format: Tino Wilson Sanchez, Kwame Agyeman, Saied Mirshahidi, Nathan Wall, Colwick Wilson, Susanne Montgomery, Carlos A. Casiano. Identification of alpha-enolase and annexin as candidate tumor-associated antigens by immunoseroproteomic profiling of autoantibodies in African American and Caucasian men with prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1831. doi:10.1158/1538-7445.AM2015-1831

Cancer-associated serum autoantibodies are generally considered as “sensors” of molecular events associated with tumorigenesis, and thus constitute promising biomarkers for cancer detection and management, as well as tools for the identification of novel oncoproteins. Immunoseroproteomics is a standard approach for the identification of serum autoantibodies reacting with tumor-associated antigens (TAA) in human cancer populations. This approach entails using one- and two-dimensional gel electrophoresis of proteins from aggressive PCa cell lines, coupled with immunoblotting and mass spectrometry, to characterize the anti-TAA antibody repertoire in a given patient. Immunoseroproteomics has been applied mostly to cancer patients of European and Asian ancestry, and has not been used in African American (AA) patients with PCa. AA men show a disproportionately high incidence and mortality of PCa, compared to other ethnic groups, and display more aggressive tumors developing at a younger age. Recent epidemiological studies suggest that after adjusting for socioeconomic and health care-related factors, these disparities still persist, pointing to biological factors as contributors to these disparities. Growing evidence indicates that genes associated with immune function and autoimmunity are dysregulated in prostate tumors from AA compared to Caucasian (CC) men. This prompted us to initiate an immunoproteomic analysis of the anti-TAA autoantibody response in AA and CC men with PCa. We hypothesize the anti-TAA autoantibody response might be greater in AA patients with PCa, and that it could be used to identify novel blood biomarkers for early screening and management of the disease. In initial studies, we screened aggressive PCa cell lysates with serum samples from AA (n=39) and CC (n=50) men. Early results showed the autoantibody response in the AA cohort had a greater autoantibody frequency and reactivity than the response in CC patients. Immunoproteomic analysis of select AA sera revealed alpha-enolase, fumarate hydratase, and annexin A11 as candidate TAAs in PCa. These proteins have been implicated in previous PCa studies. Additional validation will come from determining the frequency of the autoantibody response and the expression of candidate TAAs in PCa tissue microarrays. We are currently expanding our immunoseroproteomics analysis to sera from a larger cohort (n>200) of AA men and CC men (n>100) with and without PCa, stratified by age and cancer stage. Comparing the anti-TAA repertoire between AA and CC men with and without PCa will aid in the customization of TAA arrays for autoantibody profiling and lead to the identification of promising biomarkers for early PCa detection and monitoring of tumor progression in AA populations. Our approach may also help identify unique immunoserological signatures in AA and CC men to reveal biological determinants of PCa health disparities. Citation Format: Tino Wilson Sanchez, Saied Mirshahidi, Nathan Wall, Susanne Montgomery, Colwick Wilson, Carlos A. Casiano. Immunoseroproteomic profiling of autoantibodies to tumor associated autoantigens in African American and Caucasian men with prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2502. doi:10.1158/1538-7445.AM2014-2502

In the context of health preventive behaviors, apart from issues related to HIV and AIDS, studies about alcohol, tobacco and other drugs and violence, young African American men are one of the least understood and most underserved populations in the US. Mostly due to lack of insurance they are known to have limited access to health care, and rarely engage in preventive health care or preventive health behaviors. Yet we know that as a group, just some short years later, they will present with high rates of chronic diseases such as diabetes, heart disease and smoking related diseases and many will prematurely die. In addition, recent research suggests high levels of undiagnosed depression in this group of men and links this to their lack of control and stressful lives. In fact many argue that maladaptive behaviors such as drug use and unprotected sexual activity are indeed ways of self medicating such depression. Generally, African-Americans in low-income neighborhoods experience high levels of chronic stress due to oppressive social and economic conditions. In addition, the neighborhoods in which many of these young men reside are crowed, have high levels of violence, are poorly maintained, and generally do not offer opportunities for good nutrition or safe daily activities. With emergent clarity about the associations between socioeconomic status, chronic stress, and depression in the development of chronic disease, we need to direct more efforts toward developing culturally specific interventions that actively and respectfully engage these young men as partners and move them along to a more health conscious lifestyle. Using community based participatory research methods we worked in partnership with a group of young African American men between ages 18 to 30, recruited from community sites in a low income urban southern California community. Using theoretical sampling and triangulation for respondent selection, we conduct exploratory Grounded Theory-based interviews (N=15) and validation focus groups exploring men's knowledge, beliefs, practices and barriers related to lifestyle changes, chronic disease, stress, and prevention. In a follow-up survey based on socio-ecological theory and our qualitative results we then explored feasibility and logistics for future preventive interventions. Results indicate a general lack of knowledge about health and the health consequences of various types of behaviors that were highly prevalent; low perceived vulnerability to disease at present and for the future; high levels of stress, stressful life events and undiagnosed depression; as well as low perceived control over their life circumstances. Men also shared with us a surprisingly high level of interest in preventive interventions if delivered respectfully and in the context of their commitment to finding ways to improve their lives. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 971.

Statement of purpose: Breast cancer is the most common cancer in American women and the second leading cause of cancer death in women. Despite scientific gains, not all segments of the U.S. population have benefited from advances in the prevention and treatment of breast cancer. Although breast cancer mortality has declined by 31% in California, age-adjusted mortality rates are significantly higher in women from the Inland Empire (IE) compared to the California average for 2003-2007, and were particularly high for non-Hispanic Black women. Roughly, 2 million women live in the IE, which spans over 27,000 square miles. The female population includes 43% Hispanics, 41% non-Hispanic Whites, 7.2% non-Hispanic Blacks and 5.4% Asian Pacific Islanders. The purpose of this study was to identify factors that contribute to the unequal burden of breast cancer among minority women in the IE and to use this information to help reduce breast cancer incidence, morbidity and mortality. Methodology: Two data sets were analyzed, a convenience sample of 230 African American (AA) breast cancer survivors and volunteers from the IE and a random sample of 107 AA breast cancer patients, survivors and advocates from the IE who participated in a descriptive analytic study that evaluated knowledge, attitudes and practices toward breast cancer clinical trial participation. Data was analyzed in SPSS 16.0. Data on breast cancer statistics was obtained from the 11th and 14th Desert Sierra Cancer Surveillance Program (DSCSP) of the Region 5 of the California Cancer Registry and the IE affiliate of Susan G Komen for the Cure 2009 Community Profile Report. More than 90% of the DSCSP women are from the IE. Results: The 2003-2007 age adjusted mortality rate for invasive breast cancer was 25.4 for the IE women, which is significantly higher than the California average of 22.8. The death rate for DSCSP Black women was 34.3 compared to 27 for White women. Approximately 11.6% of households in the IE had income below poverty level and 24% of females, mostly African American and Latina, aged16-64 were uninsured. Approximately 60% of the respondents were not educated about breast health and among women 40 and over, 71% did not have a mammogram in the last year. TV/media news coverage, mostly from the Los Angeles area, was a poor local health educational tool. Nearly 80% of the women were willing to participate in breast cancer clinical trials but were not given opportunities to do so. Conclusion: The incidence and mortality patterns, combined with poverty, lack of medical insurance and breast health education reveal the tragedy produced by a failure to detect breast cancer in the early stage in AA and Latina women in the IE. The pattern of lower risk of pre-invasive and invasive breast cancer accompanied by higher risk of death from breast cancer are consistent with a failure to provide early detection and state-of-the art treatment for this target population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 986.