bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B024: Racial differences in financial toxicity among metastatic breast cancer patients
Authors: Samuel Cleo A. , Spencer Jennifer C. , Manning Michelle L. , Rosenstein Donald L. , Reeder-Hayes Katherine E. , Sellers Jean B. , Wheeler Stephanie B.
Published: August 2020

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR07) of the Conference Proceedings.

Citation Format: Cleo A. Samuel, Jennifer C. Spencer, Michelle L. Manning, Donald L. Rosenstein, Katherine E. Reeder-Hayes, Jean B. Sellers, Stephanie B. Wheeler. Racial differences in financial toxicity among metastatic breast cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B024.
Abstract B044: PVT1 exons 4A and 4B overexpressed in prostate cancer in black males regulate prostate epithelial cell proliferation and migration
Authors: Pal Gargi , Ogunwobi Olorunseun
Published: August 2020

Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the United States, accounting for approximately 13% of cancer-related deaths. PCa is also the leading cancer in terms of incidence and mortality in men from Africa and the Caribbean. PCa is a multifactorial, complex disease, with the exact mechanisms for its development and progression unclear. Understanding the molecular mechanisms underlying the development and progression of PCa is necessary. This will aid in the discovery of novel and efficacious biomarkers with applications in early PCa detection and molecular therapeutic targeting. The non-protein coding gene locus Plasmacytoma Variant Translocation (PVT1) is located at 8q24 and is overexpressed in PCa. PVT1 has at least 12 exons that make separate transcripts having different functions. We have recently shown that PVT1 exons 4A and 4B are significantly overexpressed in prostate cancer tissues of Black males and are potential clinical biomarkers for prostate cancer in Black males. In this study, the role of PVT1 exons 4A and 4B in the migration and proliferation of prostate epithelial cells was examined. PVT1 exons 4A and 4B gene fragments were cloned into plasmid expression vectors and transfected into the RWPE1 prostate epithelial cell line to examine their effect on prostate epithelial cell proliferation and migration. We observed that overexpression of either PVT1 exon 4A, or PVT1 exon 4B significantly increased prostate epithelial cell migration and proliferation. This indicates that PVT1 exons 4A and 4B are functional biomarkers for prostate cancer. Better understanding of the roles of PVT1 exons 4A and 4B in PCa may lead to the future possibility of exploiting them for diagnosis, therapy, and other clinical applications in PCa.

Citation Format: Gargi Pal, Olorunseun Ogunwobi. PVT1 exons 4A and 4B overexpressed in prostate cancer in black males regulate prostate epithelial cell proliferation and migration [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B044.
Abstract B045: Exosomal microRNAs are associated with prostate cancer aggressiveness in African American patients
Authors: Ali Hamdy E.A. , Gaballa Rofaida , Sholl Andrew S. , Gaballah Mohamed , Bustamante Juan J. , Zanwar Preeti , Ali Hamed I. , Abd Elmageed Zakaria Y.
Published: August 2020

Background: The morbidity and mortality rates of prostate cancer (PCa) in African American (AA) are 2-3 times higher than European American (EuA) men. The molecular mechanisms underlying the aggressiveness of PCa have not fully identified. Thus, our aim was to evaluate the diagnostic/prognostic utility of exosomal microRNAs (miRs) to classify PCa patients according their race and aggressive phenotype in AA patients. Their functional role in tumor aggressiveness was also determined.

Methods: Exosomes were isolated from the conditioned media of AA and EuA PCa cell lines. The expression of miRs was validated in exosomes, free-circulating plasma, and FFPE tissue specimens of forty AA and EuA patients using quantitative real-time PCR analysis. The sensitivity and specificity of exosomal miRs to classify prostate cancer patients according their race and aggressiveness were assessed using receiver operating characteristic (ROC) curve analysis. To study the functional significance of exosomal miRs, cell proliferation, clonogenic, cell cycle and migration assays were performed in PCa cells transfected with miR-3128.

Results: Differential expression of exosomal miR-3613-3p, miR-3218, miR-3679, and miR-3680 was demonstrated in the plasma of AA versus EuA of PCa patients. While exosomal miR-3613 and miR-3679 (p<0.05) were upregulated, free-circulating miRs downregulated (p<0.05) in the plasma of AA versus EuA patients. The accuracy of miR-3679 to discriminate AA from EuA was improved when combined with the other three miRs (AUC jumped from 0.717 to 0.897). Intriguingly, miR-3128 showed a dual role in AA versus EuA cells. Overexpression of miR-3128 increased the cell growth in AA cells while it did the opposite in EuA cells. These data were recapitulated by migration, cell cycle and clonogenic assays.

Conclusion: Our findings underline the role of exosomal miRs in health disparity of PCa. The differential expression of miRs in AA men demonstrates their reliability as biomarkers and their potential role in promoting tumor aggressiveness in

AA men.

Citation Format: Hamdy E.A. Ali, Rofaida Gaballa, Andrew S. Sholl, Mohamed Gaballah, Juan J. Bustamante, Preeti Zanwar, Hamed I. Ali, Zakaria Y. Abd Elmageed. Exosomal microRNAs are associated with prostate cancer aggressiveness in African American patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B045.
Abstract B063: Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York
Authors: Robine Nicolas , Froeling Fieke , Hubert Benjamin , Zody Michael C. , Oschwald Dayna , Varmus Harold , Sawyers Charles , Tuveson David
Published: August 2020

Recent advances in DNA sequencing technologies have revolutionized approaches to the prevention, risk assessment, early detection, diagnosis, and treatment of cancers. However, many ethnic groups, especially nonEuropean populations, have been significantly underrepresented in cancer research, including clinical trials, and have not received equal benefits in clinical practice. As a result, our current knowledge about tumor biology, cancer risk, and response to treatment has primarily been derived from patients of European descent. These inequities limit our understanding of the many types of cancer and may exacerbate health disparities in the United States. In this proposal, we address both the scientific and social issues by creating a dynamic research platform within the greater New York area that promises to enhance the ways in which cancer is prevented, diagnosed, and treated. This initiative, named Polyethnic-1000, will involve patients and staff at several academic health centers and partner hospitals in the New York City region. It will use the genomics and informatics capabilities of the New York Genome Center to determine how inherited and somatically acquired genetic variations affect the behavior of cancers occurring in ethnically diverse populations. In a first, retrospective phase, we will establish the workflow from sample acquisition to whole-exome and RNA sequencing, data analysis, and data sharing within the consortium. Then we will start a prospective study enabling the formation of cohorts of interest for particular cancer types and particular ethnicities, with uniform consent allowing broad data sharing of the somatic variants identified. Polyethnic-1000 will establish a framework to enhance interactions among our region's academic and health centers to advance cancer genomics. These efforts should improve and widen the use of genomics for all, especially currently underserved ethnic minority populations.

Citation Format: Nicolas Robine, Fieke Froeling, Benjamin Hubert, Michael C. Zody, Dayna Oschwald, Harold Varmus, Charles Sawyers, David Tuveson. Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B063.
Abstract B069: Ecological model links proto-oncogene to high susceptibility of Blacks to TRPV6-expressing metastatic cancers
Authors: Hilliard Constance B.
Published: August 2020

Introduction: This ecological model traces the etiology of a certain class of metastatic cancers, which kills Blacks at more than twice the rate of Whites. These malignancies, defined by the uncontrolled proliferation of TRPV6 mRNA in mutagenic tissue, include metastatic prostate cancer, triple-negative breast cancer, and colorectal and ovarian cancer. This study will show that the cause is an ethnic-specific haplotype of the TRPV6 calcium ion channel. This proto-oncogenic African TRPV6a variant is more calcium absorbent than the non-African/European TRPV6b allele. African-Americans inherited strong bones from their low-calcium-consuming (200-400 mg/day) Niger-Kordofanian West African ancestors. However, American Blacks are maladapted to the high-calcium food environment of the U.S. This research shows that the ancestral TRPV6a allele can become invasively oncogenic when overexposed to free calcium ions, leading to the aforementioned class of cancers.

Methods: Analyses of the incidence of TRPV6-expressing cancers in Blacks and Whites as a function of dietary consumption are conducted.

Results: These data show a direct correlation between levels of calcium intake in Blacks, who carry the ancestral TRPV6a calcium ion channel, and incidence of the following hormonal cancers: metastatic prostate cancer, triple-negative breast cancer, colorectal cancer and ovarian cancer.

Summary: Because the African TRPV6a calcium ion channel variant is more absorbent of free calcium ions than its non-African counterpart, this ecological model shows that carriers of this variant are at increased risk of metastatic prostate cancer, triple-negative breast cancer, and ovarian and colorectal cancers, when exposed to high-calcium food environments.

Conclusions: Hypersensitivity to Ca2+ triggers certain metastatic cancers in Blacks, characterized by the upregulation of TRPV6 transcript. Lidocaine and SOR-C-13, a peptide derived from the saliva of the short-tail shrew, are identified as potential TRPV6 calcium channel inhibitors.

Citation Format: Constance B. Hilliard. Ecological model links proto-oncogene to high susceptibility of Blacks to TRPV6-expressing metastatic cancers [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B069.
Abstract B072: Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells
Authors: Godfrey Sherette , Rorie Checo
Published: August 2020

Understanding the relationship between heavy metal exposure and triple-negative breast cancer cells may help to elucidate the high breast cancer mortality rate and health disparity in African-American women, as they may be exposed to these heavy metals at higher rates and/or their cells may react more negatively to the heavy metals when compared to their Caucasian counterparts. Triple-negative breast cancer (TNBC) accounts for about 15% of all breast cancers and is characterized by cancer cells that lack the expression of estrogen, progesterone, and HER2/Neu receptors. For this reason, TNBC cells do not respond to hormone therapies or HER2/Neu targeted treatments. The human body utilizes some metals in small amounts as micronutrients; however, many metals such as cadmium-2, chromium-6, arsenic, lead, and mercury that are introduced to the body are not needed physiologically. Human exposure to trace metals in higher-than-needed amounts or exposure to nonessential metals can cause damage to the body as they can be toxic or even carcinogenic. Here we expose the TNBC cell line HCC 1806 to Cadmium-2. While less is known about the long-term carcinogenic potential of cadmium exposure in the broader population and for other organs, evidence suggests its potential association to lung, breast, and endometrial cancer and mortality. Previous lab data revealed that exposure to high concentrations of Cadimum-2 ions causes a differential cytotoxic cell death response in TNBC cells and demonstrates different genotoxic targets and implications in their mutagenic potential when HCC 1806 cell lines were exposed to this ion. Here, the cell line HCC 1806 has been treated with 5 ug/ml of Cadmium-2 ion, revealing increased toxicity using the lactate dehydrogenases assay (LDH), decreased viability (MTS assay), and flow cytometry reveals an abrogation of the cell cycle. The LDH assay revealed that the cells exposed to cadmium resulted in a P-value less than 0.0001 and assay data present percent cytotoxicity of 5.1 and 10.7, respectively, for control and treated cells. The MTS assay alongside trypan blue exclusion assay demonstrated a trend of decreasing viability among the treated cells. The flow cytometric analysis revealed an increase in the S-Phase in the cadmium treated cells compared to the controls. These results are potentially early indicators of a molecular effect of Cd ions on breast cancer cells that could elucidate the role that cadmium may play in promoting the aggressive behavior of TNBC or could potentially lead to future treatment regiments.

Citation Format: Sherette Godfrey, Checo Rorie. Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B072.
Abstract B092: Promoting HPV vaccination among adolescent girls in Ghana, West Africa: A case study
Authors: Cudjoe Joycelyn , Cudjoe Dora , Brakatu Bernard Fiifi
Published: August 2020

Background: Cervical cancer remains one of the leading causes of cancer-related death among Ghanaian women. Although there are vaccines available to protect women against human papillomavirus (HPV), the virus that causes cervical cancer, the use of cervical cancer screening and prevention services among Ghanaian women remains low. In addition, many people in Ghana still reside in areas where access to health care services such as vaccinations and cancer screening is limited.

Description: Gavi, the Vaccine Alliance, established a pilot HPV vaccine program to provide subsidized HPV vaccines to young girls living in low-income countries with a high cervical cancer burden. To be eligible, countries must demonstrate their capacity to vaccinate more than 50% of young girls between ages 9-13 years living in an average-sized district or community. In November 2013, the Ghanaian government partnered with Gavi to provide subsidized vaccines to over 6,000 girls living in seventeen districts in the Greater Accra, Central and Northern regions.

Lessons Learned: Lack of political commitment is a challenge to the successful implementation of the HPV vaccine program in Ghana. Financial uncertainty, logistical problems such as poor infrastructure, lack of public buy-in, and the lack of relevant scientific data to inform decision making are threats to the successful implementation of the HPV vaccine initiative in Ghana.

Conclusion: To improve vaccination coverage rate, we recommend that the Ghanaian government commits to making HPV vaccination a health priority. Community participation and buy-in must be strengthened through active advertisement and outreach programs. This case study has also given an indication of the importance of further studies on the burden of cervical cancer in Ghana and cost effectiveness of an HPV vaccine initiative.

Note: This abstract was not presented at the conference.

Citation Format: Joycelyn Cudjoe, Dora Cudjoe, Bernard Fiifi Brakatu. Promoting HPV vaccination among adolescent girls in Ghana, West Africa: A case study [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B092.
Abstract B093: Cervical cancer screening among Blacks: A comparative analysis from the 2010-2014 National Health Interview Surveys
Authors: Cudjoe Joycelyn
Published: August 2020

Background: Pap testing has decreased cervical cancer incidence in the United States. However, persons of African descent are disproportionately burdened and experience worse health outcomes due to underutilization of screening services.

Purpose: Identify and compare the prevalence of Pap smear testing among African-American (AA), African immigrant (AI) and Afro-Caribbean (AC) women living in the United States.

Methods: A retrospective study was conducted using the 2010-2014 National Health Interview Survey data. Females of African descent, aged of 21-65, categorized into the 3 subgroups were included. We analyzed the prevalence of ever receiving Pap test and performed multivariate logistic regression to compare the likelihood of Pap testing among the 3 groups.

Results: Total of 3,740 respondents comprising 3,373 (90%) AA, 163 (4%) AI and 204 (6%) AC. 92% of AA reported Pap testing in the past, compared to 86% AC and 68% AI. After adjusting for age, marital status, insurance, education and income, the odds of Pap testing were 86% lower among AI [OR: 0.14,] and 56% lower among AC women [OR: 0.44] than AA.

Conclusion: This study highlights importance of addressing cancer screening needs of each subgroup separately. Studies on the impact of culture on the subgroups' screening behaviors are needed.

Note: This abstract was not presented at the conference.

Citation Format: Joycelyn Cudjoe. Cervical cancer screening among Blacks: A comparative analysis from the 2010-2014 National Health Interview Surveys [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B093.
Abstract B120: [Advocate Abstract] Let's create a generation of proactive consciousness
Authors: Hardy Fred
Published: August 2020

My mission is to narrow the scope of confusion that the lack of information concerning cancer that can devastate so many families because of late or undetected or lack of awareness and to promote a proactive attitude toward one's own health. This will be accomplished by talking to people about cancer screening, disseminating information, encouraging people to be proactive and stay on top of their health, and referring people to Karmanos to get checked. For example, conversations can be started by asking men if they know their PSA number, or about how their general health is, or about their family history of cancer. In the African American community men will often not go to the doctor if they feel healthy.

Note: This abstract was not presented at the conference.

Citation Format: Fred Hardy. [Advocate Abstract] Let's create a generation of proactive consciousness [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B120.
Abstract C018: Disparity subtyping: Bringing precision medicine closer to disparity science
Authors: Rao J. Sunil , Yu Huilin , Dazard Jean-Eudes
Published: August 2020

The genomics revolution also spawned the dawn of precision medicine. As in the National Research Council definition, if its promise is fully realized, then more accurate decisions about individual patient treatment decisions and outcomes will be possible. Disparities researchers have also begun looking to the precision medicine paradigm with the hope that some incorporation of its principles will allow for a more focused and precise path forward to reduce population disparities. While the emphasis may switch to populations from individuals, central to the paradigm still is the ability to classify individuals into subpopulations who differ in meaningful ways with respect to underlying biology and outcomes. Identification of these subpopulations is an active area of precision medicine research. For instance, there are countless papers on molecular subtyping of various cancer phenotypes. How to do such a thing in disparity science has proven elusive since it requires identifying disparity subpopulations, which is a somewhat abstract concept. In this paper we present two different strategies—level set identification and peeling. The former is based on a recursive partitioning algorithm combined with clustering of similar partitions; the latter adopts a strategy of sequentially searching for and then extracting extreme difference subgroups in a population. Using series of simulation studies and then also studying various cancer outcomes from The Cancer Genome Atlas (TCGA) repository, we demonstrate that such disparity subtypes can indeed be found, characterized, and then validated on test data.

Citation Format: J. Sunil Rao, Huilin Yu, Jean-Eudes Dazard. Disparity subtyping: Bringing precision medicine closer to disparity science [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C018.
Abstract C021: Affective mechanisms of stress-induced cigarette craving: Considerations of sex and ethnicity
Authors: Erblich Joel , Montgomery Guy H. , Schnur Julie B. , Ragin Camille
Published: August 2020

Cigarette smoking continues to be the number one modifiable risk factor for the development of cancer. Among the major impediments to successful smoking cessation are strong cravings to smoke, especially during times of heightened stress. Affective responses to stress (e.g., acute anxious and depressed mood) may serve as important mediators of cigarette cravings that are amenable to intervention. Experimental models have been developed to induce cravings reliably during stress under laboratory conditions, permitting a closer examination of possible changes in affect that may be driving cigarette cravings. The possibility that specific types of affect may be responsible for cigarette cravings, however, has not been investigated. Another key limitation of the extant research is its reliance on samples of predominantly male Caucasian smokers. Although several recent studies suggest possible sex- and ethnicity-based differences in affective responses to acute stress, no studies have explored how such differences may contribute to cigarette cravings. To that end, we conducted an experimental study in which an ethnically diverse sample of healthy volunteer female (n=163) and male (n=139) nicotine-dependent smokers were exposed to a mild stressor (guided imagery of painful dental work). We assessed positive affect (happy, relaxed, energized), negative affect (anxious, depressed, emotionally upset), and cigarette craving immediately before and after the imaginal dental stressor. Mean age of the sample was 38.6 (+ 10.2). Participants reported smoking an average of 19.5 (+ 9.8) cigarettes per day for an average of 18.9 (+ 10.0) years. Path analyses revealed that the acute stressor induced significant increases in negative affect and decreases in positive affect (p's < 0.0001). In turn, increases in anxious, but not depressed mood, mediated effects of the stressor on cigarette craving. Bootstrapped confidence intervals indicated that indirect mediated effects were significant at the 0.05 level. Interestingly, effects were particularly pronounced in women (85% of total effect for women vs. 65% of total effect for men). Among Hispanic (n=81) smokers, elevations in depressed mood mediated increases in cigarette craving (p <0.05), unlike among African American (n=138) and Caucasian (n=62) smokers. Results highlight the importance of considering sex and ethnicity when developing interventions to manage stress-induced cigarette cravings among smokers attempting to quit.

Citation Format: Joel Erblich, Guy H. Montgomery, Julie B. Schnur, Camille Ragin. Affective mechanisms of stress-induced cigarette craving: Considerations of sex and ethnicity [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C021.
Abstract C030: Gastric tumors from Latino patients show extensive intratumor heterogeneity
Authors: Toal Ted , Polanco-Echevery Guadalupe M. , Sahasrabudhe Ruta , Estrada Ana , Bohorquez Mabel , Echeverry Magdalena , Torres Javier , Carvajal-Carmona Luis G.
Published: August 2020

Gastric cancer (GC) is the 2nd leading cause of cancer-related death worldwide, with a five-year survival rate lower than 30%. GC is diagnosed in 25,000 Americans each year, with Latinos twice as likely to succumb compared to non-Hispanic whites. Treatment is currently limited to only two molecularly guided therapies. The Cancer Genome Atlas (TCGA) data show that 70% of GC patients have a mutation in a gene targetable with existing drugs. Significant spatial mutational intratumoral heterogeneity (ITH) has been identified in a variety of tumor types to date, although a GC ITH study has yet to be investigated. ITH is an important consideration for personalized therapy. Driver gene mutations are frequently found to be nonclonal, a crucial factor when assessing effective druggability. The goal of the present study was to examine GC ITH in Latino GC patients using targeted multiregional sequencing (MSEQ). Two to five biopsies from different tumor regions and adjacent normal tissue were obtained from 34 GC patients; DNA was extracted from the tumor and the normal tissues and the coding regions of 783 cancer genes were sequenced using Agilent enrichment and Illumina sequencing. Somatic mutations were called in each tumor sample, using joint analysis of all samples for each patient. Tumor cell fractions were estimated for each mutation in each sample, and phylogenetic trees were made for visualize each patient's somatic mutational patterns. We found a high degree of ITH, both intratumoral and interpatient, with the fraction of functional somatic mutations that are clonal ranging from 0 to 52%, the fraction private to one tumor sample ranging from 48% to 94%, and the fraction shared between multiple but not all samples ranging from 0 to 21%. There was at least one known drug interaction with a gene containing a clonal functional mutation for 11 of the 16 samples, and in 6 samples there were two or more known drug interactions. Our study is the first one to assess ITH in GC, and our results are important to understand the clonal architecture of these GCs and to improve molecular diagnostics.

Citation Format: Ted Toal, Guadalupe M. Polanco-Echevery, Ruta Sahasrabudhe, Ana Estrada, Mabel Bohorquez, Magdalena Echeverry, Javier Torres, Luis G. Carvajal-Carmona. Gastric tumors from Latino patients show extensive intratumor heterogeneity [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C030.
Abstract C045: Polymorphism in CYP1B1 increases CRC risk in Puerto Rican individuals that consume processed meats
Authors: Perez-Mayoral Julyann , Perez-Hernandez Maria E. , Stern Mariana , Cruz-Correa Marcia R.
Published: August 2020

Colorectal cancer (CRC) is the 1st cause of cancer-related deaths in Puerto Rico (PR). CRC is a heterogeneous disease with lifestyle and environmental factors shown to modify the risk to develop this disease. High intake of red and processed meats was determined to be a risk factor for increased risk of CRC. Genetic variations in genes involved in the metabolism of meat carcinogens have been found to be associated with CRC risk and to vary across racial/ethnic populations. The objective of this project was to determine the association of functional genetic variants in meat-carcinogen metabolism genes with CRC risk in the PR population. First, we analyzed the allelic frequencies of SNPs in key meat carcinogen metabolism genes (CYP1A1, CYP1B1, NAT2 and CYP2E1), that were previously reported to have an association with development of colorectal adenomas or CRC were evaluated in the 1000 Genomes Populations. The 1000 Genomes populations included AFR (African Populations), EUR (European Populations), CLM (Colombians from Medellin, Colombia), MXL (Mexican Ancestry from Los Angeles USA), PEL (Peruvians from Lima Peru) and PUR (Puerto Ricans from Puerto Rico). Then, we genotyped using TaqMan technology 5 functional SNPs localized at key meat carcinogen detoxifying genes, CYP1A1, CYP1B1, NAT1, NAT2 and CYP2E1 in Puerto Ricans (205 CRC cases and 218 controls). Our preliminary results showed that the allelic frequencies of the SNPs differ between PUR and the other 1000 Genomes populations, suggesting that these SNPs might have a distinct effect on the association of red/processed meat intake and CRC risk on Puerto Ricans. Furthermore, genotyping analysis showed that individuals with the AA genotype at the rs1800440 SNP (CYP1B1) who consume processed meat 2-4 times per week were at increased risk of CRC (p=0.008). These preliminary data support a role for genetic variants in genes that play key roles in the mechanisms of meat carcinogenesis as possible modifiers of the carcinogenic effects of meat.

Citation Format: Julyann Perez-Mayoral, Maria E. Perez-Hernandez, Mariana Stern, Marcia R. Cruz-Correa. Polymorphism in CYP1B1 increases CRC risk in Puerto Rican individuals that consume processed meats [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C045.
Abstract C050: Deleterious coding variants in African American Hereditary Prostate Cancer Study (AAHPC) families
Authors: Lewis Deyana D. , Wong Shukmei , Baker Angela S. , Bailey-Wilson Joan E. , Carpten John D. , Cropp Cheryl D.
Published: August 2020

Purpose: Prostate cancer is the most common cancer in males, with a ~1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ~33% of the familial risk. A portion of the undefined risk may be due to rare susceptibility variants. The African American Hereditary Prostate Cancer (AAHPC) Study, established in 1997, enrolled 77 African American families from seven clinical sites across the United States. The aim of this study is to identify rare, predictive, deleterious variants through exome sequencing of 99 cases from families selected from the AAHPC families and three 1000 Genome controls.

Methods: To explore the contribution of rare variation in coding regions to prostate cancer risk, we sequenced the exomes of 99 AAHPC cases at a mean coverage of 30x. Post-variant calling quality control (QC) was implemented using Golden Helix SVS 8 software with filters set for removal of variants with Read Depth >10, Quality Score >10, and Quality Score: Read Depth Ratio > 0.5. Mendelian inconsistency was checked using PLINK. Prioritization of all candidate genes/variants was evaluated using online databases 1000 Genome and bioinformatics tool ANNOVAR for non-reference allele frequency and predictions of functional impact.

Conclusions: Through exome sequencing of 99 AAHPC cases and three 1000 Genome controls, we identified 37 nonsynonymous single-nucleotide variants that are considered damaging by at least one predictive scoring tool in our candidate genes. Interesting candidate variants were found in known cancer susceptibility loci BRCA2, MSR1, PCNT, STAT3, WRN and ZFHX3. Future results are pending additional QC and analyses to determine which variants are shared by related individuals within each family compared to those not seen in the controls.

Citation Format: Deyana D. Lewis, Shukmei Wong, Angela S. Baker, Joan E. Bailey-Wilson, John D. Carpten, Cheryl D. Cropp. Deleterious coding variants in African American Hereditary Prostate Cancer Study (AAHPC) families [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C050.
Abstract C066: Epigenetics and inflammatory environment may contribute to racial disparities in colorectal cancer
Authors: Ma Y.M. , Roy S.K. , Srivastava R.K. , Shankar S.
Published: August 2020

Colorectal cancer (CRC) mortality rates dropped by half in the past three decades, but CRC continues to demonstrate racial disparities in incidence and survival. It is believed that unfavorable socioeconomic conditions may lead to an inflammatory phenotype. Furthermore, epigenetic events play a major role in regulating inflammatory genes that have been linked to CRC health disparities. The objective of the study was to identify gene(s) that are dysregulated in CRC using The Cancer Genome Atlas (TCGA) database, and, furthermore, to characterize those genetic event(s) that are associated with CRC health disparities. The Engrailed-2 (En2) gene encodes for a homeobox-containing transcription factor regulating embryonic brain development. The data indicate that Nanog, IL-8, and EN2 were upregulated in colorectal cancer. EN2 was highly expressed in CRC stem cells and cell lines but its expression was very low or absent in normal cells. EN2 gene was highly expressed in CRC tissues derived from African American patients compared to those from Caucasian Americans. The expression of EN2 significantly increased with patients' age. There was no difference in EN2 expression between males and females of CRC patients. Higher expression of EN2 was correlated with poor survival of CRC patients with greater IL-8 expression. EN2 may act as a novel prognostic biomarker for CRC. Our data indicate that CRC disparities may be associated with epigenetic factors regulating the inflammatory environment.

Citation Format: Y.M. Ma, S.K. Roy, R.K. Srivastava, S. Shankar. Epigenetics and inflammatory environment may contribute to racial disparities in colorectal cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C066.
Abstract C070: Social determinants of health disparities in triple-negative breast cancer in Louisiana
Authors: Hossain Fokhrul , Danos Denise , Gilliland Aubrey , Leonardi Claudia , Ferguson Tekeda , Simonsen Neal , Yu Qingzhao , Prakesh Om , Scribner Richard , Miele Lucio
Published: August 2020

Introduction: Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. TNBC patients have generally high risk of recurrence and metastasis, and treatment options remain limited, as there are no effective targeted therapies available. In USA, TNBC is diagnosed disproportionately more frequently in African American (AA) women than in European American (EA) women. We set out to investigate the role of social determinants in racial disparities in TNBC.

Methods: TNBC patients diagnosed in Louisiana from 2010-2012 were identified from the Louisiana Tumor Registry. Patients were geocoded to census tract of residence at time of diagnosis. Census tract population and socioeconomic measures were obtained from the US Census American Community Survey. We used multilevel statistical models to analyze the role of neighborhood concentrated disadvantage index (CDI), a robust measure of physical and social environment, in racial disparities in TNBC incidence, stage at diagnosis, and stage-specific survival for the study population. CDI scores were calculated according to the PhenX Toolkit protocol.

Results: We identified 1,216 women with TNBC for the study. Controlling for age, we found that AA women had a 2.21-fold risk of TNBC incidence compared to EA in Louisiana. Results from multivariate analyses indicated that the incidence of TNBC was independent of neighborhood CDI, as was the racial disparity. However, CDI did explain existing racial disparities in both stage at diagnosis and stage-specific survival. The odds of diagnosis at later stages were 42% higher for black women. A single standard deviation increase in CDI increased the hazard of breast cancer-related death by 19%. Overall, our results suggest that the increased incidence of TNBC in black women is independent of CDI, while neighborhood environment has a greater impact than race on the promotion and progression of the disease. The socioeconomic disadvantage experienced by black women coupled with increased biologic risk for TNBC contribute to the large racial disparity in breast cancer mortality in Louisiana. Further research is needed to determine the mechanisms through which social determinants affect the promotion and progression of this disease and guide efforts to improve overall survival.

Citation Format: Fokhrul Hossain, Denise Danos, Aubrey Gilliland, Claudia Leonardi, Tekeda Ferguson, Neal Simonsen, Qingzhao Yu, Om Prakesh, Richard Scribner, Lucio Miele. Social determinants of health disparities in triple-negative breast cancer in Louisiana [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C070.
Abstract C108: Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ
Authors: Liu Ying , Colditz Graham
Published: August 2020

Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of preinvasive neoplastic lesions in the breast. Black women with DCIS are more likely than White counterparts to subsequently develop invasive cancer in either breast. We examined the association between race and the risk of developing aggressive invasive breast cancer, characterized with hormone receptor (HR) negativity (both estrogen receptor and progesterone receptor negative) or intermediate-to-high risk Oncotype scores (≥18) in HR-positive subtypes, in women with DCIS.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) data, we identified 133,705 women with DCIS diagnosed between 1990 and 2015, and 12.9% were black. Cox proportional hazards regression was used to estimate relative risks (RRs) of subtypes of subsequent invasive breast cancer in either breast and metastatic breast cancer.

Results: During a median follow-up of 90 months, 6889 women developed invasive breast cancer and 6384 had HR status available. The risks of HR-defined (Pheterogeneity=0.0004) and Oncotype score-defined (Pheterogeneity=0.046) invasive breast cancer subtypes after initial DCIS significantly varied by race. The RR of HR-negative invasive breast cancer was 1.86 (95% CI 1.57-2.20) and the RR of subsequent invasive subtypes with intermediate-to-high Oncotype scores was 1.29 (95% CI 1.00-1.67) in Black women with DCIS, which was independent of age, pathologic features and treatment. In women who had data on HR status in both primary DCIS and subsequent invasive breast cancer, the HR discordant rate was higher in Black patients than in White patients (21.2% versus 18.9%, P=0.003), which was largely driven by HR loss (15.4% versus 9.5%). Black race was more strongly associated with HR loss (RR=1.92, 95% CI 1.41-2.61, Pheterogeneity=0.03) than HR concordance (RR=1.24, 95% CI 1.09-1.41) and HR gain (RR=1.04, 95% CI 0.67-1.62).

Conclusions: Black women with DCIS had higher risks of developing aggressive invasive breast cancer compared with White counterparts, which may contribute to their worse survival. Future studies examining biologic differences in the progression of DCIS for Black patients are warranted.

Citation Format: Ying Liu, Graham Colditz. Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C108.
Abstract C119: [Advocate Abstract] Health equity through meditation interventions
Authors: Nalls W. Erika
Published: August 2020

Meditation and mindfulness are current buzz words and there has been evidence-based research for their relevance and efficacy in alleviating distress amongst cancer patients/survivors and their families. My questions are around how to create culturally sensitive mindfulness/meditation/prayer interventions for certain vulnerable populations who lives intersect with the realities of race, class/economic status and rural/urban status that create barriers to well-being on the spectrum of a cancer experience. The barriers that are created are real. How do these (additional component of stress/distress) contribute to distress as defined by NCCN guidelines? What does this distress look like when compounded with these multiple (often simultaneously interacting) realities and how can meditation/mindfulness/prayer address these challenges? As a nontraditional researcher, I am interested in how to create collaborative interventions that center answers in the synergistic spaces of dialogue (call and response) between research communities and local communities and multidirectional dialogue. It requires cooperation, dialogue and a nuanced cognition which centers well-being.

Citation Format: W. Erika Nalls. [Advocate Abstract] Health equity through meditation interventions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C119.
Abstract IA09: Colorectal cancer in Louisiana: Disparities in incidence, mortality, and access to screening
Authors: Karlitz Jordan J.
Published: August 2020

Louisiana has the fourth highest colorectal cancer incidence and third highest mortality rate in the country. Within the state of Louisiana, wide disparities exist with regard to colorectal cancer incidence, mortality, and access to screening tests. In this session, epidemiologic data will be explored in order to better understand these disparities and strategies will be discussed to decrease colorectal cancer rates and maximize access to life-saving screening tests, including colonoscopy and stool-based testing.

Citation Format: Jordan J. Karlitz. Colorectal cancer in Louisiana: Disparities in incidence, mortality, and access to screening [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA09.
Abstract IA21: Assembling study cohorts for molecular characterization from medically underserved populations: A view from the trenches
Authors: Gardner Kevin L.
Published: August 2020

Gathering relevant high-quality clinical data and biologic material to support cancer health disparities research in underserved populations can be a challenging task. During this session, I will briefly outline approaches that my group employs in collaboration with a small oncology center in rural North Carolina and pathologists at the Aga Khan University Hospital, Nairobi, Kenya, to study breast cancer cohorts. The discussion will include: 1) recruiting and engaging pathologists for tissue analysis; 2) using digital pathology and automated scoring platforms to increase throughput, accuracy, and reproducibility; 3) incorporation of real-time telepathology workflows to provide histopathology consultation, classifications, scoring, and validation; 4) dealing with missing data; and 5) recruiting and working with an informatics team for data abstraction from the medical records.

Citation Format: Kevin L. Gardner. Assembling study cohorts for molecular characterization from medically underserved populations: A view from the trenches [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA21.