bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB_C16: Long-read sequencing reveals alternative splicing driven, shared immunogenic neoepitopes regardless SF3B1 status in uveal melanoma
Authors: Shen Jianfeng , Zhang Zhe
Published: December 2023

Tumor-specific neoepitopes are promising targets in cancer immunotherapy. However, identification of functional tumor-specific neoepitopes remains challenging. In addition to the most common source single-nucleotide variants (SNVs), alternative splicing (AS) represents another rich source of neoepitopes and can be particularly useful to certain cancers with low SNVs such as Uveal melanoma (UM). UM, the most prevalent adult ocular malignancy, has poor clinical outcomes due to a lack of effective therapies. Recent studies have manifested the promise of harnessing tumor neoepitopes to treat UM. Notably, previous studies have focused on neoepitope targets associated with mutations in splicing factor 3b subunit 1 (SF3B1), a key splicing factor, however little is known about the neoepitopes that are commonly shared by patients but independent of SF3B1 status. To identify the AS-derived neoepitopes regardless SF3B1, we herein used a comprehensive Nanopore long-read-sequencing approach to elucidate the landscape of AS and novel isoforms in UM. We also performed high-resolution mass-spectrometry to further validate the presence of neoepitope candidates, and analyzed their structures using AlphaFold2 algorithm. We experimentally evaluated the anti-tumor effects of these neoepitopes, and found they induced profound immune responses by stimulating interferon (IFN)-g production and activating T-cell-based UM tumor killing. These results provide novel insights into UM-specific neoepitopes independent of SF3B1, and lay the foundation for developing therapies by targeting these actionable neoepitopes.

Citation Format: Jianfeng Shen, Zhe Zhang. Long-read sequencing reveals alternative splicing driven, shared immunogenic neoepitopes regardless SF3B1 status in uveal melanoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C16.
Abstract LB_C20: A tumor-associated chemokine attracts CCR4-expressing CD4+ cells to foster immune repression and tumor aggressiveness in MYCN-driven neuroblastoma
Authors: Qin Xiaodan , Lam Andrew , Zhang Xu , Sengupta Satyaki , Iorgulescu J. Bryan , Das Sanjukta , Zhou Zhenwei , Zuo Tao , Meara Grace K. , Rager Madison , Floru Alexander E. , Ni Hongru , Kemet Chinyere , Veerapaneni Divya , Kashy Daniel , Lin Liang , Lloyd Kenneth , Kwok Lauren , Smith Kaylee S. , Nagaraju Raghavendar T. , Meijers Rob , Ceol Craig , Liu Ching-Ti , Alexandrescu Sanda , Wu Catherine J. , Keskin Derin B. , George Rani E. , Feng Hui
Published: December 2023

Neuroblastoma, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. Here we combined analyses of human neuroblastoma with live tracking and functional studies of the tumor microenvironment (TME) in zebrafish. We identified a tumor-associated chemokine (TAC) as a key driver of MYCN-mediated immunosuppression and neuroblastoma aggression. Taking advantage of in vivo zebrafish models of MYCN-driven neuroblastoma that resemble human high-risk disease, we demonstrated that TAC overexpression in zebrafish neural crest cells induces an immunosuppressive TME while promoting rapid tumor onset and progression.  We also demonstrated that as early as the premalignant stage, tumor cells secrete TAC to attract CCR4-expressing Cd4+ cells to induce immunosuppression and tumor aggression. In addition, genetically depleting Cd4+ T regulatory cells abolishes the immunorestrictive and pro-tumorigenic effects of TAC. We showed that human MYCN-activated neuroblastoma upregulates and secretes TAC, which is a reliable predictor of poor patient survival. Analysis of primary patient samples demonstrates a strong positive association between MYCN and TAC expression in neuroblastoma cells together with the enrichment of FOXP3+ T cells in the TME.  Our work provides the first example that MYCN can activate TAC to allure CD4+ immune cells to the TME and incite immunosuppression, positioning TAC as a potential novel immunotherapeutic target for the treatment of MYCN-driven high-risk neuroblastoma.

Citation Format: Xiaodan Qin, Andrew Lam, Xu Zhang, Satyaki Sengupta, J. Bryan Iorgulescu, Sanjukta Das, Zhenwei Zhou, Tao Zuo, Grace K. Meara, Madison Rager, Alexander E. Floru, Hongru Ni, Chinyere Kemet, Divya Veerapaneni, Daniel Kashy, Liang Lin, Kenneth Lloyd, Lauren Kwok, Kaylee S. Smith, Raghavendar T. Nagaraju, Rob Meijers, Craig Ceol, Ching-Ti Liu, Sanda Alexandrescu, Catherine J. Wu, Derin B. Keskin, Rani E. George, Hui Feng. A tumor-associated chemokine attracts CCR4-expressing CD4+ cells to foster immune repression and tumor aggressiveness in MYCN-driven neuroblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C20.
Abstract A010: Community dissemination and application training: Approach developed for research teams working with Native Nations and Native American urban communities
Authors: Teufel-Shone Nicolette I. , Goldtooth-Begay Carol , Begay Andria
Published: December 2023

Trusted, sustained collaborations with Native American communities requires regular communication on research intention, process and outcomes. In the National Cancer Institute funded Native American Cancer Prevention Partnership (NACP), many research teams were not familiar with strategies to provide updates and outcomes to community audiences in Native American communities. The NACP Outreach Core used a 3-stage communication framework: 1) identification of components to consider, e.g., audience demographics, primary message, and communication channels; 2) practice in context, ideally with community partners or advisors; and 3) deliberative practice when knowledge and skills have been formed. The Outreach Core modified the Kellogg Foundation’s “Elements of a Strategic Communication Plan”, to develop a 3-hour training composed of didactic and interactive sessions, entitled Community Dissemination and Application Training (C-DAT). After the workshop, a one-hour technical assistance session was scheduled with each research team and Outreach Core members to discuss and guide the team’s community dissemination plans. The unique modifications made to create C-DAT included: 1) the research team’s obligation to develop and share clear messages, given the historic mistrust and miscommunication with Native Nations; 2) the importance of convening community advisors and/or to pilot draft materials to assure cultural appropriateness; and 3) the use of communication channels familiar and accessible by the intended audience.  In addition, the Outreach developed a Directory for Reaching Relatives Using Media (DRRUM) that provides contacts and needed information on regional Native Nation or Native serving newsletters/newspapers and radio stations to support the dissemination process.  To date, research teams have developed short videos, contributed to the NACP podcast series, designed an independent website and provided presentations at community centers.  The impact of these efforts cannot be evaluated given information was widely broadcast o a variety of platforms.  The frequency and locale of the downloads of the on-line resources indicate that audiences in Native American Urban communities and Native Nations, especially in rural areas, are interested in learning about the activities addressing cancer prevention in their communities.  

Citation Format: Nicolette I. Teufel-Shone, Carol Goldtooth-Begay, Andria Begay. Community dissemination and application training: Approach developed for research teams working with Native Nations and Native American urban communities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A010.
Abstract A029: LGBTQ+ health navigation panel: Discussing barriers and facilitators in navigation to services for immigrant and non-immigrant LGBTQ+ community members in New York City area
Authors: Trifonov Alexandr , Moore Kevin , Haseltine Megan C. , Domogauer Jason
Published: December 2023

Background: Patient navigation plays a crucial role both in patient care management and overcoming barriers to care. Navigating the complexities of US healthcare is difficult for everyone, including individuals who are native to the US as well as newly arrived immigrants and refugees from across the world. The LGBTQ+ community is greatly affected by a multitude of health disparities. Discrimination, stigma, bias, and prejudice towards the LGBTQ+ community contribute to those health disparities, which makes the role of LGBTQ+ health navigation even more essential. Patient advocacy and support in finding proficient clinical and social services is the core of LGBTQ+ patient navigation. The authors of this abstract will create a discussion-based panel to share experiences and tailored approaches that have successfully helped in navigating LGBTQ+ patients, addressing social determinants of health, creating inclusive environments, and contributing to LGBTQ+ proficient care.  Methods: LGBTQ+ Health Navigation Panel will consist of several LGBTQ+ health advocates, navigators, and/or policymakers from healthcare and community-based institutions from across New York City area. They will participate in a discussion-based session model, which will be moderated by one of the authors of this abstract.  Discussion: This LGBTQ+ patient navigation panel will focus on discussing healthcare services and navigation support for immigrant and non-immigrant LGBTQ+ community members in the New York City area. Services that we would focus on will be physical, mental, and social health, as well as patient advocacy and community education. In addition, a significant portion of our discussion will include topics of cancer prevention, screening, diagnosis, treatment, and survivorship in the LGBTQ+ community.

Citation Format: Alexandr Trifonov, Kevin Moore, Megan C. Haseltine, Jason Domogauer. LGBTQ+ health navigation panel: Discussing barriers and facilitators in navigation to services for immigrant and non-immigrant LGBTQ+ community members in New York City area [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A029.
Abstract A041: The iCCARE Consortium for Prostate Cancer in Black men: Evaluability assessment of the implementation of a care plan for black prostate cancer survivors
Authors: Bonner Timethia , Ashing Kimlin , Odedina Folakemi
Published: December 2023

Despite notable progress in early detection, prevention, and treatment of prostate cancer within the United States, racial disparities are present very early in the patient journey of Black men, starting with the shared decision-making process. The disproportionately higher number of Black men diagnosed with prostate cancer also suggests that Black men must also contend with the management of associated physiological and psychosocial symptoms. The survivorship care plan was designed to communicate critical information that cancer survivors and their health care advocates need as a guidebook for long term post treatment care, and improved survivorship. An associated systematic literature review conducted by our multidisciplinary investigative team revealed there was a severe underutilization of survivorship care plans within cancer survivorship care especially with Black men. The considerable lack of utilization and/or tailoring of survivorship care plans may be a significant contributor to the worsening of health disparities in this population. Co-designing survivorship care plans with key stakeholders, specifically Black survivors and their health care advocates, is imperative to ensure that the plan meets the needs and preferences that Black men have for survivorship care. This presentation will discuss the steps the investigative team used to address the disparities in shared decision-making, and the subsequent underutilization of survivorship care plans. The investigative team utilized semi-structured interviews and focus group methodology to explore how the lived experiences of Black male prostate cancer survivors are incorporated and addressed in the construction and contents of a culturally tailored survivorship care plan (CaP_SCP- Black Men). An evaluability assessment was conducted to determine whether implementation of the newly created survivorship care plan is feasible, appropriate, and addresses the specific needs of the population before full implementation. This presentation will discuss how this combination of approaches allowed the investigative team to understand how survivorship care plans affect the unique complexities of survivorship in Black men, and allows for the feasibility study of  the implementation of a culturally relevant survivorship care plan (CaP_SCP- Black Men) in a population that bears the greatest burden nationally and globally.    

Citation Format: Timethia Bonner, Kimlin Ashing, Folakemi Odedina. The iCCARE Consortium for Prostate Cancer in Black men: Evaluability assessment of the implementation of a care plan for black prostate cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A041.
Abstract A042: Community advisory board members’ perspectives on genetic literacy and patient-caregiver communication of prognostic genomics for localized prostate cancer
Authors: Cobran Ewan K. , Turner Jocelyn , Odedina Folakemi , Bryce Alan H. , Williams Christopher , Rodriguez Jose , Williams Roger , Nathan Woodrow , Bryant Thomas , Nathan LoveVonia , Husband Laureen
Published: December 2023

Background: The National Comprehensive Cancer Network (NCCN) recommends the use of tissue-based genetic tests, such as Decipher, Prolaris, and Confirm mdx for localized prostate cancer, to help patients and caregivers make more informed treatment decisions at the time of diagnosis. However, while much enthusiasm currently exists for the burgeoning field of genomic medicine, prostate cancer disparities continue to persist in underserved communities despite the existence of evidence-based treatment guidelines. Methods: A diverse 15-member Community Advisory Board (CAB) representing rural and urban communities in Duval County, Florida were recruited from May to June 2023, to build a community-academic partnership, for the development and implementation of a genetic literacy patient-caregiver educational intervention for localized prostate cancer. The 15-member CAB was divided into groups of 5 for focus group discussions. Qualitative and quantitative data from CAB members were integrated to gain better understanding of the facilitators and barriers for prostate cancer genetic literacy in underserved communities. Results: The thematic analysis reveals several key themes related to prostate cancer, screening, treatment, and genetics. These themes reflect the diverse perspectives and experiences of the CAB members regarding prostate cancer, ranging from personal anecdotes to broader societal issues. Participants expressed thoughts related to fear, lack of knowledge, cultural beliefs, and access to healthcare. The discussion on prostate cancer and tissue based genetic testing highlighted the complexities surrounding prostate cancer and the need for further education, awareness, and access to affordable healthcare for all individuals at risk. Conclusion: CAB members emphasized the importance of improving access to information, promoting education, and addressing cultural barriers to ensure that individuals are informed about available options for prostate cancer diagnosis and treatment.

Citation Format: Ewan K. Cobran, Jocelyn Turner, Folakemi Odedina, Alan H. Bryce, Christopher Williams, Jose Rodriguez, Roger Williams, Woodrow Nathan, Thomas Bryant III, LoveVonia Nathan, Laureen Husband. Community advisory board members’ perspectives on genetic literacy and patient-caregiver communication of prognostic genomics for localized prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A042.
Abstract A099: Higher proportions of racial and ethnic minority cancer survivors experience health-related social needs compared to non-Hispanic cancer survivors in the All of Us Research Program
Authors: Smith JoAnn , Tesfaye Samantha , Mendoza Martin , Sanchez Janeth
Published: December 2023

Background: Cancer survivors are at a greater risk of experiencing financial hardship and unmet health-related social needs (HRSN), such as food or housing insecurity, after a cancer diagnosis. HRSN has been associated with lower access, utilization, and delivery of timely quality cancer care and poorer cancer-related outcomes. Cancer survivors experiencing HRSN may also be less likely to engage and participate in research (e.g., clinical trials). As the most diverse cohort worldwide, the All of Us Research Program provides a unique opportunity to better understand the prevalence of HRSN among cancer survivors. The purpose of this study is to characterize the proportion of All of Us cancer survivors experiencing food and housing insecurity and identify potential differences across racial and ethnic populations. Results: We identified a total of 37,146 All of Us cancer survivors out of 412,211 core participants. Of these, the majority self-identified as non-Hispanic White (84%), 4% as non-Hispanic Black, 4% as Hispanic, 2% as multiracial, and <1% self-reported as Asian, Native American/American Indian, Native Hawaiian/Pacific Islander, or Middle Eastern/North African. Among cancer survivors, 5.5% stated being worried about running out of food and 4.4% stated that their food didn’t last and did not have money to get more. While only about 1% of cancer survivors stated moving more than once within the last 12 months, 6.1% stated that they worried about not having a place to live and 16% experienced at least one poor housing quality characteristic (e.g., mold, water leak, or bug infestation). There was a significant difference in the proportion of cancer patients who reported food and housing insecurity across racial and ethnic populations (p<0.001), with a higher proportion of cancer survivors from racial and ethnic groups underrepresented in biomedical research experiencing these HRSN. Conclusion: While less than 6% of cancer survivors in the All of Us Program experienced food or housing insecurity, the proportion of racial and ethnic minority populations experiencing these HRSN was higher compared to non-Hispanic White cancer survivors. Future research should assess the impact of experiencing HRSN on research participation and health related outcomes within the All of Us Research Program.

Citation Format: JoAnn Smith, Samantha Tesfaye, Martin Mendoza, Janeth Sanchez. Higher proportions of racial and ethnic minority cancer survivors experience health-related social needs compared to non-Hispanic  cancer survivors  in the All of Us Research Program [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A099.
Abstract B034: Characterization of a dual steroid 3β-,17β-oxidoreductase in the gut bacterium Eggerthella lenta
Authors: Binion Briawna J. , Gaskins Rex , Ridlon Jason
Published: December 2023

As of 2023 there are over 200,000 new cases and over 30,000 deaths caused by prostate cancer with African-American (AA) men having a higher incidence then other ethnicities according to the American Cancer Society. Although numerous therapeutic methods are used to treat prostate cancer such as hormone therapy, radiation therapy, chemotherapy, and chemical castration, prostate cancer often becomes metastatic resulting in death with the five year survival rate for AA men presenting with castration resistant prostate cancer (CRPC) being ~ 32%. Androgen production is known to be the main driver of CRPC progression. Researchers are baffled as to why this progression is taking place after patients have received a combination of these therapeutic methods to stop androgen production and metabolism. Eggerthella lenta has a long history as an important bile acid and steroid metabolizing gut microbial species. We and others have previously published on the extensive oxidation and epimerization of bile acid hydoxyl groups. Previous work demonstrated that E. lenta may be involved in the conversion of 17-keto steroids to testosterone. By cloning, expressing, and purifying genes predicted to encode pyridine nucleotide-dependent oxidoreductases from E. lenta DSM 2243, we identified a recombinant enzyme with dual 3beta, 17beta-hydroxysteroid dehydrogenase activity. We performed kinetic analysis on both 5alpha-reduced bile acids ("allo"-bile acids) and 5alpha-reduced steroids. There is a paucity of work at present on gut bacteria that metabolize the 17beta-hydroxy group on steroids, so this observation demonstrates that a unique enzyme in the gut microbiome can alter host steroids. These findings are consistent with the possibility that gut or urinary tract bacteria may contribute to CRPC.

Citation Format: Briawna J. Binion, Rex Gaskins, Jason Ridlon. Characterization of a dual steroid 3β-,17β-oxidoreductase in the gut bacterium Eggerthella lenta [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B034.
Abstract B061: Nonalcoholic fatty liver disease (NAFLD) polygenic risk score and risk of hepatocellular carcinoma in a multiethnic population
Authors: Sadeghi Homa , Bogumil David , Conti David V. , Haiman Christopher , Marchand Loïc Le , Setiawan Veronica Wendy
Published: December 2023

Purpose:  Hepatocellular carcinoma (HCC) is the third cause of cancer mortality globally, with 10%-12% of cases attributable to nonalcoholic fatty liver disease (NAFLD). Genetic variants included in NAFLD polygenic risk scores (PRS) have been associated with HCC risk. Since these associations have been studied primarily among European ancestry populations, in the current study we assessed the transportability of a NAFLD PRS associated with HCC risk in a racially/ethnically diverse population. Methods: We conducted a nested case-control study including 275 incident HCC cases and 73,045 controls from the Multiethnic Cohort Study, using a 21-variant PRS for NAFLD created based on prior GWAS and replication studies on MEC participants and other populations. Associations between PRS (per standard deviation) and HCC were estimated using logistic regression adjusting for age, sex, and global ancestry. A stratified analysis was conducted by body mass index (BMI) due to the direct relationship of obesity with NAFLD and HCC.  Results: The PRS was associated with HCC risk in the combined sample (ORper SD= 1.84, 95% CI: 1.64-2.06). Signifcant associations were observed in Japanese Americans [ORper SD=2.26 (1.87-2.72)], Latinos [ORper SD=1.89 (1.52-2.35)], Native Hawaiians [ORper SD=1.84 (1.26-2.69)], and with the associations being weaker and non-significant in whites [ORper SD=1.33 (0.92-1.93)] and African Americans [ORper SD=1.25 (0.90-1.75)]. The PRS association was stronger among those with BMI >= 25 kg/m2 for the combined sample (ORper SD :2.46, 95% CI:1.92-3.14), (P heterogeneity <0.0001); and all racial/ethnic groups [Latino: 3.01(1.88-4.81), African American: 2.72 (95% CI: 1.18-6.27), Hawaiian: 2.25 (1.17-4.32), Japanese: 2.13 (1.36-3.36), and White:2.11(1.10-4.04)]. Conclusion: A NAFLD PRS is applicable for HCC risk prediction across racial/ethnic populations. BMI may modifiy this PRS-HCC risk association.  

Citation Format: Homa Sadeghi, David Bogumil, David V. Conti, Christopher Haiman, Loïc Le Marchand, Veronica Wendy Setiawan. Nonalcoholic fatty liver disease (NAFLD) polygenic risk score and risk of hepatocellular carcinoma in a multiethnic population [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B061.
Abstract B067: Markers of vitamin D3 activity in normal breast tissue and subsequent breast cancer: A pilot study
Authors: Ebersole Anastasia , German Rana , Cote Michele L.
Published: December 2023

Vitamin D3 (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)), has been hypothesized to be associated with breast cancer initiation and progression through several different mechanisms. In addition to playing a key role calcium and phosphate homeostasis, it has been shown to be involved in various processes associated with carcinogenesis, including immune modulation, proliferation, and cellular differentiation.  Population-based studies have consistently shown circulating levels of vitamin D3 are lower among African American populations compared to other racial and ethnic groups in the United States.  Epidemiologic evidence is mixed as to whether circulating vitamin D3 levels are associated with risk of developing breast cancer, with a recent meta-analysis reporting null results.  Fewer reports examine the association between tissue-based markers of vitamin D3 metabolism and breast cancer risk.  Here, we seek to determine whether the target of vitamin D3, the Vitamin D Receptor (VDR), and vitamin D3 synthesizing and degrading enzymes (CYP24A1, CYP27B1, respectively) are present in normal breast tissue, and if so, whether presence in the tissue is associated with risk of subsequent breast cancer.  We utilized tissue specimens from the Susan G. Komen Tissue Bank at Indiana University to determine the expression of VDR, CYP24a1 and CYP27b1 in tissue from healthy, cancer-free donors. We selected n=14 women who developed a subsequent breast cancer, age, self-reported race and ethnicity-matched to n=28 women who did not develop cancer.  Healthy breast tissue from n=4 men were also included, although results are preliminary and will only be described. Immunohistochemistry (IHC) was performed for VDR (Cell Signaling), CYP24A1 (Invitrogen) and CYP27B1 (Santa Cruz Biotechnology) on the formalin-fixed, paraffin-embedded tissue.  Slides will be scored by a breast pathologist to determine the amount and intensity of the staining.  Descriptive statistics will be used to summarize donor characteristics and IHC markers, including results stratified by self-reported race.  Correlations between IHC markers will also be assessed. Logistic regression models will be performed to determine if an association exists between VDR, CYP24A1, CYP27B1 and development of breast cancer.  Understanding the protein expression of normal breast tissue in those who do and do not develop breast cancer may identify pathways amenable to prevention strategies.

Citation Format: Anastasia Ebersole, Rana German, Michele L. Cote. Markers of vitamin D3 activity in normal breast tissue and subsequent breast cancer: A pilot study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B067.
Abstract B084: Neighborhood environment and occurrence of crown-like structures in breast tissues of a diverse cohort of women with and without breast cancer
Authors: Lawrence Wayne , Lenz Petra H. , Dorsey Tiffany , Ambs Stefan , Lord Brittany , Harris Alexandra R. , Franklin Jamirra G.
Published: December 2023

Neighborhood features have been shown to influence breast cancer risk and outcomes, but there is a lack of molecular data in this area. Our study seeks to investigate whether neighborhood deprivation factors such as employment, housing, poverty, residential stability, and residential segregation by race/ethnicity may influence the presence of inflammation in the breast, scored as crown-like structures of the breast (CLS-B). We hypothesize that high deprivation leads to an increase in inflammatory processes that promote a pro-inflammatory immune microenvironment, including CLS-B presence and the activation of cancer-related pathways, especially for Black women who often experience more aggressive tumors and worse breast cancer outcomes. Our study included 104 normal samples from reduction mammoplasty (63 Black, 41 White) and 114 tumor adjacent normal tissues (73 Black, 41 White) from the NCI-MD Breast Cancer Study. All participants completed a detailed questionnaire to capture breast cancer risk factors of interest and demographic characteristics. Tract-level socioeconomic deprivation was measured using a neighborhood deprivation index (NDI). Tissue samples underwent immunohistochemical staining for the pan-macrophage marker, CD68, in order to detect CLS-B. Pathologists used an artificial intelligence-assisted approach to score CLS-B for whole slide images. Preliminary findings in a subset of 36 participants indicate a positive association between presence of CLS-B and increased NDI scores in a linear regression model adjusted for age (b=1.29, p=0.28). This preliminary work provides an initial link between neighborhood environment and inflammatory markers within breast tissue. On-going efforts are focused on expanding our sample size to further bolster these findings, supporting future mechanistic investigations.

Citation Format: Wayne Lawrence, Petra H. Lenz, Tiffany Dorsey, Stefan Ambs, Brittany Lord, Alexandra R. Harris, Jamirra G. Franklin. Neighborhood environment and occurrence of crown-like structures in breast tissues of a diverse cohort of women with and without breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B084.
Abstract B122: Association between allostatic load and prostate-specific antigen (PSA) levels in African American men
Authors: Chevrin Jamirah Y. , Kittles Rick
Published: December 2023

Introduction: To further understand cancer health disparities, researchers are utilizing the framework of social determinants of health with a significant factor including physiological factors such as stress. Emerging evidence suggests physiological dysregulation such as high allostatic load to have negative health effects including acting as a driver to cancer risk and development. Understanding the lifetime effects of allostatic load levels within the African American populations is imperative. However, the literature is sparse on allostatic load and prostate cancer in African American men despite high rates of allostatic load and prostate cancer in this population. The goal was to evaluate the association of high allostatic load and prostate cancer within African American men in Chicago. Methods:  In 2003-2012, 1200 AA men, over 18 years of age were recruited through yearly community health events in Chicago, Illinois. Allostatic load was defined as the sum of 8 established baseline risk-associated biomarkers, cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, creatinine, blood urea nitrogen, high-density lipoprotein, low-density lipoprotein, that exceeded specified cut off points adapted from verified scales found in previous literature. Results: The presence of high allostatic load levels was significantly associated with elevated PSA levels in Black men. Participants with high allostatic load scores were 2 times more likely to have elevated PSA levels. [Odds Ratio (OR) 2.129 (95%CI 1.254, 3.614)] Conclusion In conclusion, these results suggest the biological toll of stress in Black men may contribute to higher PSA scores and prostate cancer risks. It is important to understand the complex interplay of the multi-factorial experiences that are unique to Blacks in the United States that may put Black men at higher risk for factors that drive prostate cancer. Further research should be conducted on understanding these socio-biological risk factors to develop effective intervention strategies.  

Citation Format: Jamirah Y. Chevrin, Rick Kittles. Association between allostatic load and prostate-specific antigen (PSA) levels in African American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B122.
Abstract B131: Social drivers of adverse health outcomes among cancer survivors
Authors: Telles Victoria M. , Banegas Mateo , Strong David
Published: December 2023

Purpose of the Study Disparities in health outcomes among cancer survivors are often driven by differences in social-ecological resources. Poor health outcomes and multiple chronic conditions often manifest as a result of shared demographic and social risk factors. The aim of this study was to examine the social drivers that predict adverse health outcomes among cancer survivors. Methods Data from the national longitudinal Population Assessment of Tobacco and Health (PATH) Study was used to examine social drivers of several adverse health outcomes: tobacco use, sleep trouble, high cholesterol, diabetes, and high blood pressure among cancer survivors enrolled in the first cohort (waves 1-3; n=1924). Social drivers included education, financial stress, poverty level, insurance status, and satisfaction with social relationships. Survey-weighted multivariable logistic regression was used to assess demographic and social drivers that predicted health outcomes among cancer survivors. Results Among the 1,924 cancer survivors, most were non-Hispanic, White (77%); 56% female; ages ranged from 18-34 (14%), 35-54 (27%), 55-64 (24%), 65+ (34%). Higher tobacco use was linked (p’s<0.05) to both demographic (males, younger) and social drivers (lower education, poverty, lack of insurance and social dissatisfaction). Trouble sleeping was associated with social drivers including financial stress (p<.001) and social dissatisfaction (p<.0001). High cholesterol was significantly associated with demographics (older age) and social drivers including lower education, access to insurance, and social dissatisfaction (p’s<.05). High blood sugar was significantly associated with demographics (older age, NH Black) and social drivers (lower education and social dissatisfaction (p’s<.05). High blood pressure was significantly associated with demographic (older age, male, NH Black) and social drivers including lower education college (p<.05) and financial stress (p<.05).  Conclusions Increased recognition of the critical role of social drivers on health outcomes suggests effective interventions that are sensitive to cancer survivors’ social-ecological contexts are needed to improve health equity and reduce cancer health disparities.   

Citation Format: Victoria M. Telles, Mateo Banegas, David Strong. Social drivers of adverse health outcomes among cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B131.
Abstract B132: Vitamin D and breast cancer health disparities: A rapid scoping review investigating the relationship between vitamin D and breast cancer mortality in African American women stratified by molecular subtype
Authors: Vaughn Adrienne
Published: December 2023

Introduction: Black women face disproportionate mortality rates from breast cancer because of being more likely to face aggressive breast cancer prognosis and metastasis. Past research findings showed that low vitamin d serum levels are a risk factor for certain types of breast cancer (TNBC, HR+ etc.). Vitamin D deficiency is particularly prevalent amongst black individuals and black women are more likely to experience metastasis and aggressive breast cancer prognosis. However, there is a lack of research on black women that investigates the relationship between vitamin d serum levels and mortality, stratified by prognosis category.   Specific Aim and Hypothesis:  This rapid scoping review is developed to describe the nature, number, and scope of published research articles measuring the association between vitamin D and mortality in black breast cancer patients based on the molecular subtype. a)     Is there a gap in literature to determine if vitamin D has an impact on mortality in black women with breast cancer? If there is an impact, does it vary based on molecular subtype in black women?   Methods: A rapid scoping review will be conducted. Studies that do not provide the following data on African American women with breast cancer will be excluded: breast cancer molecular subtype, mortality status, and vitamin d serum levels pre and post diagnosis. Articles will be reviewed if they were published after 2013 to maintain scientific relevance and must be in the English language. The databases used to conduct the search will be PubMed, Cochran, CINAHL, JBI, web of science, TRIP, and science direct. Studies will be analyzed together based on the type of study (ex. Case-control vs cohort) and when the vitamin D measurements were taken (ex. Pre-diagnosis vs post-diagnosis).   Public Health Implication Identifying potential factors such as lack of vitamin D that contribute to high cancer morbidity and mortality in black women with breast cancer will allow different mechanisms for reducing this cancer disparity.  

Citation Format: Adrienne Vaughn. Vitamin D and breast cancer health disparities: A rapid scoping review investigating the relationship between vitamin D and breast cancer mortality in African American women stratified by molecular subtype [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B132.
Abstract C002: Integrating multiomics data to identify African ancestry-informative markers acting as eQTLs in breast cancer
Authors: Boudeau Samantha
Published: December 2023

Ancestry-informative markers (AIMs) are SNPs that are found at relatively higher frequencies in a specific population and can be used to estimate genetic ancestry. Genetic ancestry is becoming more commonly used in biomedical research investigating the genetic basis of diseases. For many cancers, the literature suggests that African ancestry is associated with poor response to treatment, poorer prognosis, and poorer survival. More specifically, African American women with breast cancer are more likely to have more aggressive subtypes of the disease and diagnosed with a later stage of the disease at an earlier age compared to their European American counterparts. Some of this disparity remains after accounting for socioeconomic factors, suggesting a genetic basis for the health disparities observed in many cancers.  To evaluate the genetic basis of cancer health disparities in populations of African ancestry, we identified a set of 46,787 African ancestry informative markers (AIMs) using 1000 Genomes Project data from African and European populations. These AIMs were functionally annotated and investigated for potential associations with cancer in the literature, using tools such as VEP, SIFT, and Polyphen. Using multiomics data (RNAseq, genotype, methylation, copy number variation) from The Cancer Genome Atlas and an integrative eQTL modeling approach, we are investigating which of these AIMs act as expression quantitative trait loci in breast cancer. Of the 47K SNPs identified, 0.6% percent was found to be in the coding regions of the genome and AIMS located on chromosomes 8, 10, 11, 15, 18, and 19 were found to be associated with different cancers in the literature including breast and colorectal cancers. Approximately 5K of the AIMs were found in the TCGA breast cancer data and preliminary results identified cis-eqtls in 4 different genes including SERINC2 and ZSCAN23, and trans-eqtls in about 8 genes including CLCN3 and DEDD. These eQTL AIMs are being evaluated for potential association with ancestry-specific differential survival and response to treatment in breast cancer.

Citation Format: Samantha Boudeau. Integrating multiomics data to identify African ancestry-informative markers acting as eQTLs in breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C002.
Abstract C003: Analysis of genetic control of differential DNA methylation between breast cancer patients of African and European ancestry
Authors: Founta Kyriaki , Chambwe Nyasha
Published: December 2023

Black women with significant African ancestry experience a disproportionately higher incidence of the most aggressive and invasive breast cancer subtypes, along with worse clinical outcomes across all population groups in the United States. These health disparities arise from complex interactions between genetic, sociocultural, and environmental factors. Although there is a critical need to understand how these non-genetic factors contribute to disease risk or etiology, they are difficult to measure reliably, and their long-term impacts are not well understood. Epigenetic mechanisms that regulate gene expression, such as DNA methylation (DNAm), have been proposed to capture the molecular impact of adverse environments on tumor biology. While DNAm levels can change in response to environmental cues, they are also regulated by individual genotypes at methylation quantitative trait loci (meQTLs), presenting a challenge for modeling environmental effects on cancer molecular phenotypes. We hypothesize that ancestry differential DNAm in breast cancer can be partially explained by ancestry differential genotype frequencies of SNPs at meQTL loci. We leveraged multi-omic data from The Cancer Genome Atlas (TCGA) breast cancer (BRCA) cohort to perform integrative analysis for patients of European and African ancestry (n=578), including ancestry-based differential methylation analysis, meQTL analysis and association testing of genotypes and ancestry.  We identified 804 CpGs differentially methylated between European and African ancestry BRCA patients.  meQTL analysis at these sites identified 130 cis-meQTLs and 1,019 trans-meQTLs. ~84% of the identified cis- and ~80% of the identified trans-meQTLs show evidence of differential genotype frequencies by ancestry. Gene set enrichment analysis of the meQTL target genes implicated genes involved in regulation of cell differentiation and developmental processes, phosphatase activity and phosphorylation processes. Our findings show that ancestry specific DNAm differences display strong genetic associations via ancestry associated meQTLs (a-meQTLs) affecting fundamental biological functions in breast cancer. This result points to the potential for confounding due to genetic ancestry in studies that use DNA methylation as a molecular readout of environmental exposures.  

Citation Format: Kyriaki Founta, Nyasha Chambwe. Analysis of genetic control of differential DNA methylation between breast cancer patients of African and European ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C003.
Abstract C032: Patterns of care and patients’ outcomes for myelodysplastic syndromes in Puerto Rico: A real-world data analysis
Authors: Ortiz-Ortiz Karen J. , Ramos Tonatiuh Suárez , Castañeda-Avila Maira A. , Torres-Cintrón Carlos R. , Gierbolini-Bermúdez Axel , Tortolero-Luna Guillermo
Published: December 2023

Background: Myelodysplastic syndromes (MDS) are a group of rare blood cancers with a wide range of clinical outcomes and a highly variable prognosis. Usually, most population-based registries do not collect cancer-related biological and genetic markers, which limits the use of population-based registries to address critical research questions. We leveraged the Puerto Rico (PR) Central Cancer Registry (PRCCR) to collect this data and analyze clinical characteristics and outcomes of patients diagnosed with MDS in PR. Methods: The study population includes patients diagnosed with MDS in PR between 2015 and 2019. Descriptive statistics and frequency analysis were used to describe the variables of interest. Logistic regression models were used to examine factors associated with the use of genetic marker tests. Bivariate analyses were performed to evaluate association between treatment patterns and patients’ characteristics. Three-year survival curves were estimated using Kaplan-Meier (with log-rank test to assess differences between survival curves). Multivariable Cox regression models were used to estimate the magnitude of association between the risk of dying among patients with MDS and different genetic markers/clinical characteristics. Results: The study cohort consisted of 475 patients. Between 67.2% and 81.7% of cases reported information of laboratory tests and prognostic markers. The abnormal karyotype had the highest presence in patients with MDS among those that reported the test with 47.4%. After adjusting for variables of interest, the risk of dying in MDS patients who did not have a del(5q) or a mutation of TP53, EZH2, or NRAS was 53%-85% lower than the risk of dying in patients who had either one of the mutations (p<0.05). Almost half of the MDS patients (47.4%) received treatment and of those, almost a third (29.3%) received it within the first 30 days after the diagnosis of MDS. The most common first-course treatment was azacitidine (52.0%), followed by lenalidomide (20.0%). Patients with a very low IPSS-R had a 3-year survival of 72.8% and those with a very high IPSS-R had a 3-year survival of 7.8%. Conclusion: The data from the PRCCR confirm the prognostic value of the IPSS-R and the role of the cytogenetic and molecular abnormalities on the patient’s outcomes.

Citation Format: Karen J. Ortiz-Ortiz, Tonatiuh Suárez Ramos, Maira A. Castañeda-Avila, Carlos R. Torres-Cintrón, Axel Gierbolini-Bermúdez, Guillermo Tortolero-Luna. Patterns of care and patients’ outcomes for myelodysplastic syndromes in Puerto Rico: A real-world data analysis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C032.