Browsing by Author "Schwartz, Ann G."

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    A Review of Research on Disparities in the Care of Black and White Patients With Cancer in Detroit
    (Frontiers Media, 2021-07-07) Simon, Michael S.; Raychaudhuri, Sreejata; Hamel, Lauren M.; Penner, Louis A.; Schwartz, Kendra L.; Harper, Felicity W. K.; Thompson, Hayley S.; Booza, Jason C.; Cote, Michele; Schwartz, Ann G.; Eggly, Susan; Epidemiology, Richard M. Fairbanks School of Public Health
    Racial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute's (KCI's) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.
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    A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO
    (Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public Health
    Introduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.
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    ATR inhibition overcomes platinum tolerance associated with ERCC1- and p53-deficiency by inducing replication catastrophe
    (Oxford University Press, 2023-01-11) Heyza, Joshua R.; Ekinci, Elmira; Lindquist, Jacob; Lei, Wen; Yunker, Christopher; Vinothkumar, Vilvanathan; Rowbotham, Rachelle; Polin, Lisa; Snider, Natalie G.; Van Buren, Eric; Watza, Donovan; Back, Jessica B.; Chen, Wei; Mamdani, Hirva; Schwartz, Ann G.; Turchi, John J.; Bepler, Gerold; Patrick, Steve M.; Medicine, School of Medicine
    ERCC1/XPF is a heterodimeric DNA endonuclease critical for repair of certain chemotherapeutic agents. We recently identified that ERCC1- and p53-deficient lung cancer cells are tolerant to platinum-based chemotherapy. ATR inhibition synergistically re-stored platinum sensitivity to platinum tolerant ERCC1-deficient cells. Mechanistically we show this effect is reliant upon several functions of ATR including replication fork protection and altered cell cycle checkpoints. Utilizing an inhibitor of replication protein A (RPA), we further demonstrate that replication fork protection and RPA availability are critical for platinum-based drug tolerance. Dual treatment led to increased formation of DNA double strand breaks and was associated with chromosome pulverization. Combination treatment was also associated with increased micronuclei formation which were capable of being bound by the innate immunomodulatory factor, cGAS, suggesting that combination platinum and ATR inhibition may also enhance response to immunotherapy in ERCC1-deficient tumors. In vivo studies demonstrate a significant effect on tumor growth delay with combination therapy compared with single agent treatment. Results of this study have led to the identification of a feasible therapeutic strategy combining ATR inhibition with platinum and potentially immune checkpoint blockade inhibitors to overcome platinum tolerance in ERCC1-deficient, p53-mutant lung cancers.
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    Psychosocial factors associated with genetic testing status among African American women with ovarian cancer: Results from the African American Cancer Epidemiology Study
    (Wiley, 2022) McBride, Colleen M.; Pathak, Sarita; Johnson, Courtney E.; Alberg, Anthony J.; Bandera, Elisa V.; Barnholtz-Sloan, Jill S.; Bondy, Melissa L.; Cote, Michele L.; Moorman, Patricia G.; Peres, Lauren C.; Peters, Edward S.; Schwartz, Ann G.; Terry, Paul D.; Schildkraut, Joellen M.; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Racial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed. Methods: Data came from 270 AA women diagnosed with ovarian cancer and participating in a population-based, case-control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake. Results: One-third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000-$74,999, 2.04; 95% confidence interval [CI], 1.06-3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92-5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14-0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses. Conclusions: Consistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability.
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    Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma
    (American Association for Cancer Research, 2022) Peres, Lauren C.; Colin-Leitzinger, Christelle; Sinha, Sweta; Marks, Jeffrey R.; Conejo-Garcia, Jose R.; Alberg, Anthony J.; Bandera, Elisa V.; Berchuck, Andrew; Bondy, Melissa L.; Christensen, Brock C.; Cote, Michele L.; Doherty, Jennifer Anne; Moorman, Patricia G.; Peters, Edward S.; Segura, Carlos Moran; Nguyen, Jonathan V.; Schwartz, Ann G.; Terry, Paul D.; Wilson, Christopher M.; Fridley, Brooke L.; Schildkraut, Joellen M.; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.
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    Use of electronic cigarettes among African American cancer survivors
    (Wiley, 2023) Wharram, Christelle E.; Kyko, Jaclyn M.; Ruterbusch, Julie J.; Beebe-Dimmer, Jennifer L.; Schwartz, Ann G.; Cote, Michele L.; Medicine, School of Medicine
    Background: The use of electronic cigarettes (e-cigarettes) is increasing rapidly in the United States, although the negative health outcomes associated with these products are still unknown. Emerging research has examined the use of e-cigarettes in the cancer survivor population as a whole, yet none has focused on e-cigarette use in the African American (AA) cancer survivor population. Methods: The authors used data from the Detroit Research on Cancer Survivors cohort study, comprised of AA adult cancer survivors. Logistic regression models were used to evaluate factors potentially associated with e-cigarette ever use and current use. Results: Of 4443 cancer survivors who completed a baseline interview, 8.3% (n = 370) reported ever using e-cigarettes, and 16.5% (n = 61) of those reporting ever use also reported current use of e-cigarettes. Ever users and current users were on average younger than those who did not use e-cigarettes (57.5 vs. 61.2 years; p < .001). Current cigarette smokers were >20 times more likely (odds ratio, 20.75; 95% confidence interval, 12.84-33.55) and former smokers were almost 10 times more likely (odds ratio, 9.50; 95% confidence interval, 6.03-14.97) to have ever used e-cigarettes than never-smokers. Preliminary data suggested that ever use of e-cigarettes is associated with later stage at diagnosis for breast and colorectal cancers. Conclusions: As the use of e-cigarettes increases in the general population, it is important to continue to monitor their use in cancer survivors and to gain more insight as it pertains to the AA cancer survivor population. Elucidation of the factors associated with e-cigarette use in this population may help inform comprehensive cancer survivorship recommendations and interventions.