Cancer In African Americans Research Articles

Beyond Triple-Negative: High Prevalence of Quadruple-Negative Breast Cancer in African Americans.

Quadruple-negative breast cancer (QNBC) is a triple-negative breast cancer (TNBC) subtype that lacks expression of the androgen (AR) receptor. Few studies have focused on this highly aggressive breast cancer, portending worse survival rates. We aimed to determine the following: (1) QNBC's molecular and clinical characteristics and compare them with other subtypes and (2) QNBC's association with clinicopathological factors and prognostic markers. We performed immunohistochemical evaluations of ARs on tissue tumor microarrays from FFPE tumor blocks of invasive ductal breast carcinomas in 202 African American women. Univariate analysis was performed using the chi-square test, with survival rates calculated using Kaplan-Meier curves. Overall, 75.8% of TNBCs were AR-negative. Compared to the luminal subtypes, TNBC and QNBC tumors were likely to be a higher grade (p < 0.001); HER2+/AR- and QNBCs were also larger than the other subtypes (p < 0.001). They also expressed increasing mean levels of proteins involved in invasion, such as CD44, fascin, and vimentin, as well as decreasing the expression of proteins involved in mammary differentiation, such as GATA3 and mammaglobin. We found no association between QNBC and stage, recurrence-free survival, or overall survival rates. The high prevalence of TNBC AR-negativity in these women could explain observed worse outcomes, supporting the existence of the unique QNBC subtype.

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Abstract 5218: Genome-wide association study of African Americans reveals new susceptibility loci contributing to lung cancer and mechanisms of population-specific etiology

Abstract Lung cancer incidence and mortality in the U.S. have substantial ethnic disparities. African Americans of both sexes have the high incidence rate at 56.8 and the highest death rate at 38.1 per 100,000 people from 2015 to 2019. Non-Hispanic black men have the highest incidence at 73.9 and the highest death rate at 56.3 per 100,000 people. While many genome-wide association studies (GWAS) of lung cancer have discovered ~45 putative risk loci, a large proportion of the heritability of lung cancer remains unexplained. To date, most single population-based GWAS have been performed in Europeans while there are a few Asian ancestry-specific genetic studies and two cross-ancestry studies. Non-European GWAS of lung cancer has been underrepresented. Although African Americans have higher lung cancer incidence and poorer lung cancer survival rate, and smoke fewer cigarettes per day compared to Europeans, few comprehensive GWAS of lung cancer in African Americans has been conducted. This study aims to decipher the genetic component of predisposition to lung cancer among African Americans. This study aims to decipher the genetic component of predisposition to lung cancer among African Americans. We conducted an African-ancestry GWAS comprising 2,280 lung cancer cases and 4,301 controls to comprehensively characterize common and low-frequency lung cancer genetic susceptibility loci using HRC imputed lung cancer data. The novel variants in or near VWF on 12p13.31 (OR=1.29, P=6.93 × 10−9) for overall lung cancer and GACAT3 on 2p24.3 (0.65, 1.24 × 10−9), TRIP13 on 5p15.33 (3.49, 1.00 × 10−8), ERC1 on 12p13.33 (4.64, 6.08 × 10−9), LMAN1L (near CYP1A1) on 15q24.1 (4.25, 8.71 × 10−9) for lung squamous cell cancer were identified at a genome-wide significance level. Our GWAS of lung cancer identified five novel genetic susceptibility associations and confirmed several variants on 15q25 and 19q13. Further works are required to elucidate the possible biological mechanisms underlying these associations among lung cancer and histological subtypes in African Americans. Citation Format: Jinyoung Byun, Younghun Han, Xiangjun Xiao, Christine Lusk, Hoda J. Badr, Rayjean Hung, Ann G. Schwartz, Christopher I. Amos, INTEGRAL Consortium. Genome-wide association study of African Americans reveals new susceptibility loci contributing to lung cancer and mechanisms of population-specific etiology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5218.

Evaluation of breast tumor morphologies from African American and Caucasian patients

The primary aim of this research was to investigate potential differences of breast tumor morphologies across African American and Caucasian racial groups by utilizing machine learning (ML) and artificial intelligence (AI) methods. While breast cancer disparities can partially be attributed to social determinants of health, tumor biology also contributes to survival outcomes. The rate of breast tumor growth is largely dependent on the extracellular matrix (ECM). Current research suggests the cellular components of the ECM may vary among racial and ethnic populations, and this may contribute to the incidence of cancer in African Americans. We utilized a supervised AI method to evaluate morphological differences between African American and Caucasian breast cancer tumors. Images used for analysis were downloaded from the Cancer Genome Atlas (TCGA) biorepository stored in the NIH Genomic Data Commons (GDC) data portal. We designed an ML classifier using the AlexNet model provided in PyTorch’s torchvision package. The model was pre-trained and adapted via transfer learning resulting in a classification accuracy of 92.1% when using our breast cancer tumor image database split into 80% of training set and 20% of testing set. We interpreted the results of the AlexNet and ResNet50 models using LIME and saliency mapping as the explainers. Based on the images from our bi-racial testing set, this study confirmed significant variations of tumor and ECM regions in the different racial groups evaluated. Based on these findings, further analysis and characterization may provide new insight into disparities associated with the incidence of breast cancer.

A Systematic Review of Decipher Genomic Classifier Risk Scores for Prostate Cancer in African-Americans

Background: Prostate Cancer (PCa) is a non-cutaneous malignancy in men, and Decipher being a genomic test, has gained increasing attention in estimating the risk of developing a recurrence or metastatic PCa disease in patients. Therefore, this study is focused on evaluating the association of Decipher score risk with recurrence of prostate cancer patients based on their medical, genetic predictors, and demographics (e.g., races) by conducting a systematic review. Moreover, the study has also assessed whether Decipher score risk can be a good predictor for prostate patients’ metastasis and prostate cancer-specific mortality in men and clinical decision-making regarding patient treatment recommendations. Methods:: The research study has reviewed 74 research articles, and the systematic review results have been presented in the form of themes. The studies' review indicated that Decipher acts as a genomic metastasis signature to predict metastatic disease among patients and make better decisions about treating the disease. Moreover, this genomic test can also be used in conjunction with Magnetic Resonance Imaging (MRI) for identifying the lesions that may carry the biological potential for early metastases. Furthermore, this review also identified that treatment options for PCa might range from Adjuvant Radiation Treatment (ART) and Salvage Radiation Therapy (SRT) to Radical Prostatectomy (RP); however, the selection of treatment methodology depends upon the GC score and risk stratification. Results: The results further suggested that the occurrence of PCa is two folds greater among African- Americans (AA) men as compared to non-AA men. Thus, the increasing incidence of PCa among AA and discrimination within AA's health and socio-economic conditions plays a significant role in treating AA. In this scenario, the Decipher test score plays an essential role in making treatment decisions. Conclusion: To conclude, further trials are still required for validating the Decipher biomarkers, and scientists should enhance the decipher test ability to be run on a patient's blood samples instead of tumor tissue, which will help patients use decipher as a screening test at the asymptomatic level.

Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease.

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10−4 and 9 sites with P < 10−5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.

Abstract 649: Classics to diagnostics: Assessing EMT biomarkers in colorectal cancer prognosis

Abstract Colorectal cancer (CRC) is a second most common cause of cancer death in the United States and exhibits disparities among racial and ethnic minorities. Colon polyps are abnormal growth in the epithelium that can rapidly invade surrounding mesenchyme and metastasize to form multiple secondary tumor sites. Such Epithelial-Mesenchymal Transition (EMT) is the fundamental event that results in lower survival rate for CRC patients. Altered EMT processes are also indicative of health disparity as observed for aggressive nature of prostate cancer in African Americans. In search of potential diagnostic markers that enable us to capture this transition in situ in CRC, we focused on two major biomarkers, E-Cadherin, an epithelial specific surface protein, and Vimentin, a mesenchymal specific cellular filament component. We obtained de-identified biopsy tissues samples of different stages in CRC, classified as precancerous and cancerous, along with the normal tissues, that were collected during colonoscopies for routine histopathological evaluation. In parallel, these formalin fixed paraffin embedded tissues were immunostained for the expression of E-Cadherin and Vimentin. As expected, normal tissue specimens expressed E-Cadherin exclusively in the mucosal epithelial cells while mesenchymal cells in the stroma specifically stained for vimentin expression. Interestingly, in some precancerous and cancerous specimens, we observed vimentin-positive foci within epithelial cells that lack E-Cadherin expression. This suggests a proof-of principal that an initiation of epithelial to mesenchymal transition can be detected at the clinics by performing selective immunofluorescence staining of these markers. More importantly, such detection can be correlated with the stage of the CRC that can be very insightful for the progression of the disease. Early detection in CRC through these biomarkers to supplement histopathological evaluation is promising and would provide more predictive and detailed analysis of cancer progression in tissue samples to aid in the choice of appropriate treatment plan. The accurate pre-treatment patient evaluation is pivotal to the modern push for personalized therapy. The array of early detection biomarkers will also enhance our understanding in health disparity in CRC when a large set of samples are analyzed for these markers. Citation Format: Rohin Patel, Angelique Robertson, Anjana Saxena, Mintoo Patel. Classics to diagnostics: Assessing EMT biomarkers in colorectal cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 649.

Abstract PO-196: Oral cancer disparity among African Americans

Abstract Introduction: Oral cancer caused thousands of deaths every year. The rate of oral cancer death is higher due to the late-stage discovery of oral cancer. Cancer health disparity is prevalent in indifferent racial/ethnic groups. African Americans are the primary victim of cancer health disparity. Here we directed a comprehensive review of available literature to observe the oral cancer disparity in African Americans. Method: We used various databases such as PubMed, Google scholar, and TMC (Texas Medical Center) library in July 2020. Software used to establish literature are EndNote and Zotero software. Search terms and methods used are [Oral Cancer] AND [African Americans], [Cancer Disparity] AND [African Americans], and [Oral Cancer] AND[Racial Disparity]. We found several articles that match our criteria. After reviewing the text, a table has been generated to conclude the articles. Result: Studies show varied results. Some studies showed a higher rate of oral cancer in African Americans, and some studies show a lack of knowledge of oral cancer in African Americans. Some studies also show the decline of oral cancer in African Americans. Discussion: Studies regarding oral cancer in African Americans focus on a different topic. There should be more studies that deal with one consistent question so that we can see the cancer disparity in this population. Cancer researchers should be informed about these issues of research gap in oral cancer so that they can make an appropriate decision where to allocate funding during their investigation. Citation Format: Shabnam Bhuiyan. Oral cancer disparity among African Americans [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-196.

Analysis of the 30-Pack-Year Smoking Threshold in African Americans From an Underserved Lung Cancer Screening Program

African Americans were underrepresented in lung cancer screening (LCS) trials, despite having higher lung cancer incidence and worse outcomes compared with Caucasians. There is concern that the 30-pack-year threshold excludes some African Americans who may benefit from LCS. LCS in an underserved health care system was reviewed. Providers attested that patients met LCS criteria, including 30-pack-year history, but patients also self-reported smoking histories. Self-reported data were used to identify patients with <30-pack-year histories. Over 2 years, 784 patients self-reported sufficient data to calculate pack-years. The majority were men (57.5%), and 66.2% were African Americans. Median total years smoked was 40 (interquartile range, 30-45 years), and median pack-years was 25 (interquartile range, 15-40 pack-years). African Americans were more likely to report <30 pack-years compared with other races (P < .001). The overall incidence of lung cancer was 2.0%, and incidence was similar for those with ≥30 or <30 pack-years (2.1% versus 2.0%; odds ratio, 0.94; 95% confidence interval, 0.35-2.53; P= .902). Race was not associated with lung cancer diagnosis, but African Americans were the only race to have lung cancer if pack-years were <30. The incidence of cancer in African Americans was similar in those who reported ≥30 or <30 pack-years (2.2% versus 2.7%; odds ratio, 1.21; 95% confidence interval, 0.39-3.75; P= .740), and the 30-pack-year threshold was not associated with lung cancer diagnosis. This is the first review of LCS in African Americans who self-reported <30 pack-years. Although retrospective, these data raise concern that the 30-pack-year threshold may not be an appropriate LCS criterion in African Americans.

Skin cancer in skin of color: A cross-sectional study investigating gaps in prevention campaigns on social media

Skin cancer in skin of color: A cross-sectional study investigating gaps in prevention campaigns on social media

Abstract A111: Urine-based gene expression panels with focus on prostate cancer in African Americans

Abstract Introduction: Prostate cancer (CaP) affects 1 in 7 men in their lifetime. African American (AA) men have significantly higher incidence and mortality from CaP compared to Caucasian American (CA) men. We and others have also noted that the genes commonly overexpressed in CaP (e.g., ERG) and currently used as diagnostic markers exhibit much lower frequency and more heterogeneity in AA men. The goals of this study are to develop CaP diagnostic/prognostic marker panels that takes into account race-associated differences in molecular alterations. Here we evaluated a panel of CaP associated genes using regular (non-DRE) urine from AA and CA CaP for discriminating between high-grade (Gleason score [GS], 7-10) and low-grade disease (GS, 6) and cancer negative biopsy. Methods: The quantitative expression assay protocols have been developed for noninvasive detection of candidate genes in exosomal RNAs from regular urine. The selected genes were reverse transcribed in a single reaction using gene-specific primer pool (GSP) followed by preamplification and PCR-based assay of all target genes. Results: Regular urine exosomal RNA-based assays were developed and optimized for PSGR, DLX1, HOXC4, NKX2-3, COL10A1, HOXC6, PCA3, PCGEM1, PCAT1, CTBP1, SChLAP1, ERG and SPDEF. All markers have been evaluated in a pilot study of 72 subjects undergoing diagnostic biopsies. For AA patients a sensitivity of 88.2%, specificity of 83.3%, and AUC of 0.81 were achieved for the panel (PCA3, PCGEM1, HOXC6 and SChLAP1). Consistent with numerous studies, ERG and PCA3 panel was optimal for CA patients. Preliminary analysis showed that 3 markers were found to be associated with improved discrimination between GS7 or greater and GS6 (AUC 0.78 for ERG; AUC 0.72 for PSGR and AUC 0.72 for SChLaP1) in AA CaP. In CA patients, PCA3 gave an AUC of 0.76 for predicting high-grade from low-grade disease. Analysis of an additional 100 patients is in progress. Conclusions: Given the genomic difference of prostate cancer among different race/ethnicity, this study highlights the potential for developing CaP biomarker panels in the context of race for enhancing precision medicine through improved CaP diagnosis/prognosis Citation Format: Indu Kohaar, Sreedatta Banerjee, Yongmei Chen, Amina Ali, Jacob Kagan, Sudhir Srivastava, Jennifer Cullen, Inger Rosner, Shiv Srivastava, Gyorgy Petrovics. Urine-based gene expression panels with focus on prostate cancer in African Americans [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 A111.

Abstract IA22: A comprehensive and integrated approach to identify factors associated with aggressive prostate cancer in African-Americans: The RESPOND Study

Abstract IA22: A comprehensive and integrated approach to identify factors associated with aggressive prostate cancer in African-Americans: The RESPOND Study

Abstract A017: Using social media to communicate breast cancer risk and promote breastfeeding among pregnant African American women

Abstract Purpose of Study: Incidence rates for aggressive ER- breast cancer in African Americans have continued to increase, and epidemiologic studies (AMBER Consortium) suggest breastfeeding can reduce risks for this deadly disease. Notably, breastfeeding rates are lowest among poor, younger, and African American mothers, offering an opportunity to intervene. Health behavior theories show that perceived risk for health problems can be a motivating factor for behavior change. The purpose of this NCI R21 study was to examine the behavioral impact of a tailored intervention to disseminate new scientific findings about reducing cancer risk for African American women by breastfeeding. Methods: A multimodal approach was used to reach pregnant African American women accessing services through Women, Infant and Children (WIC), community-based organizations and OB/GYNs to invite them to participate in a tailored social media educational intervention. Recruitment was delivered using Telerivet (computer-based mobile messaging platform) and participants were connected to an automated invitation to Survey Monkey to complete eligibility, consent, and pre and post-partum surveys from smart phones. Eligible participants were randomized into a control Facebook (FB) group receiving only breastfeeding messages or an intervention FB group that received both breastfeeding and breast cancer risk reduction messages. All messaging was tailored for African American mothers. Multiple polls and FB actions were used to increase participant engagement. Results: To date, a total of 612 women were recruited, 356 were eligible, 287 women consented, 261 completed pre-surveys, and 134 have currently completed post-surveys. Participants ranged from 18-54 years of age. Preliminary results show significant differences in breast cancer risk perception with an average presurvey mean of 3.07 to a post-survey mean of 1.31 (p &amp;lt;.001). Perceived behavioral control pre- to post-birth indicates significant increases in breastfeeding self-efficacy in knowledge (p &amp;lt; .001), confidence (p =.03), support (p=.002), skills (p=.01), and ease (p=.01). Qualitative interactions were captured through participation in the FB group and intragroup analysis is ongoing. Conclusions: Results will provide crucial information to determine if risk perceptions can be transformative in creating a shift from formula-as-an-equivalent-feeding-practice to “Breast is Best” among African American women within their social context—basically creating a culture-change model. Process data on intervention methods and the potential role to effectively disseminate this new message to increase breastfeeding will be presented. Citation Format: Cassy Dauphin, Frances G. Saad-Harfouche, Maria Keller, Nikia Clark, Elisa M. Rodriguez, D'zare Triplette, Marc Kiviniemi, Deborah O. Erwin. Using social media to communicate breast cancer risk and promote breastfeeding among pregnant African American women [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 A017.

Abstract C039: Investigation of a prostate cancer genetic susceptibility candidate region on chromosome 5 in African Americans

Abstract There are well documented, marked racial disparities in prostate cancer (PCa) incidence and mortality in the United States between African American (AA) and European American (EA) men. These disparities cannot be fully explained by differences in screening or treatment differences by race, and other environmental and biological risk factors have not been well characterized. We hypothesize that racial differences in the distribution of genetic risk factors may contribute to the observed disparities. We previously identified a region on chromosome 5q35 via admixture mapping that is associated with PCa in AA men (Bock 2009). Preliminary analyses in this region suggested two loci involved in chromatin regulation, and several genes including COL23A1, TSPAN17, and GRM6. These are genes that have not been well characterized in the literature, however hints of their role in PCa can be found within previous expression studies. Here, we examine the region on chromosome 5q35 in greater depth to first confirm the observed admixture and to leverage the admixture signal within that region to identify novel variants associated with risk of prostate cancer in African Americans. To achieve the first goal, we estimated genome-wide and local ancestry across chromosome 5 in African American subjects from the Multiethnic Cohort (MEC) and an independent case control study from the Barbara Ann Karmanos Cancer Institute (KCI). Our results validated the significance of the admixture (p=7.87*10-6). However, the ancestry odds ratio from the MEC study was in the opposite direction in comparison to our original discovery analysis. Despite this difference, after combining studies via meta-analysis, we still retained a significant admixture peak on the distal portion of the chromosome 5q (p=5.47*10-4), which stretched from 152-180Mb. Overall, this effect showed that increasing European ancestry at this locus was associated with increased risk of prostate cancer. Additionally, our admixture meta-analysis uncovered a secondary peak (p=3.66*10-4) from 64-96Mb, where increased risk of prostate cancer was again associated with increasing European ancestry at this locus. We also performed association testing using the MIXSCORE approach, which is a combined test of genotype and local ancestry association. Our most significant association results were located within our primary admixture association peak, and they clustered around a locus at 173 Mb. The lead single nucleotide polymorphism (SNP) within this region was rs6885032 (MIXSCORE p=7.83*10-4). Interestingly, this SNP was identified in a genome-wide association analysis as associated with height, and a recent meta-analysis of studies from the literature confirmed an association between height and prostate cancer risk. Furthermore, this SNP was also identified as an expression quantitative trait locus (p=3.30*10-9) in the Genotype-Tissue Expression project. This convergence of findings suggests a possible mechanism for this variant on prostate cancer risk. Citation Format: Albert M Levin, Gregory Dyson, Julie L Boerner, Julie J Ruterbusch, Cathryn H Bock. Investigation of a prostate cancer genetic susceptibility candidate region on chromosome 5 in African Americans [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C039.

Abstract P2-10-11: Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications

Abstract BACKGROUND African Americans comprise 12% of the total United States population. Lifetime probability of developing cancer in African Americans is 37.55%. Lifetime probability of developing breast cancer in African Americans is 11.1%. African Americans have higher lifetime probability of dying because of breast cancer compared to Caucasians (3.3% versus 2.7%). Concerns exist that African Americans are underrepresented in trials of breast cancer medications. We sought to examine African Americans participation for pivotal breast cancer medications trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. METHODS On the basis of publicly available FDA reviews, the authors assessed enrollment of African Americans in trials supporting 9 drug approvals from 2014 to 2018. Those trials resulted in approval of medications to treat breast cancer. Prevalence-corrected estimates for the participation of African Americans were calculated as the percentage of African Americans among trial participants divided by the percentage of African Americans in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of African Americans in the trial and disease population. RESULTS A total of 22,075 patients enrolled in clinical trials, which resulted in subsequent FDA approval. The proportion of African Americans enrolled in the clinical trials that led to breast cancer medication approval in the 5-year period was 6.83%. The calculated PPR for participation of African Americans in clinical trials that led to drug approval for breast cancer was 0.29. CONCLUSIONS African Americans were under represented in trials of drugs for breast cancer. Efforts should be made to increase the proportion of participation of African Americans in clinical trials. Citation Format: Samer Al Hadidi, Martha Mims, Courtney Miller-Chism, Rammurti Kamble. Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-11.

Rates of clinically significant prostate cancer in African Americans increased significantly following the 2012 US Preventative Services Task Force recommendation against prostate specific antigen screening: A Single Institution Retrospective Study.

We determined the impact of the 2012 US Preventative Services Task Force recommendation against prostate specific antigen screening on detection rates and biopsy patterns in African American and Caucasian patients. Demographics, PSA, transrectal ultrasonography volume and pathologic data were collected on patients who underwent their first ultrasound-guided prostate biopsy between January 2007 and June 2018 at a New York City Veteran Affairs Hospital. 609 biopsies were analysed preguideline (113 per year), and 487 were analysed postguideline (81 per year). There was no significant difference in the detection rates of low, intermediate or high grade PCa in Caucasians. In contrast, AfricanAmericans were significantly more likely to be diagnosed with PCa in the postguideline group (56% pre vs 66% post, P=.016), and significantly more likely to be diagnosed with intermediate-high grade PCa (38% pre vs 47% post, P=.038). Before the 2012 USPSTF recommendation, AfricanAmerican and Caucasian patients undergoing their first biopsy were equally likely to be diagnosed with high-grade PCa (11% AA vs 11% CA). After the 2012 decision, we found that AfricanAmericans were 50% more likely than Caucasians to be diagnosed with high-grade PCa on first biopsy (10% AA vs 15% CA, P=.008). In the 6years following the 2012 USPSTF recommendation, detection rates of intermediate-high risk disease remained unchanged for Caucasian patients but have increased significantly for AfricanAmericans. The results of our study strongly support the role of routine PSA screening, particularly in higher risk patients such as AfricanAmericans.

Distribution of colorectal cancer in young African Americans: implications for the choice of screening test

We recently reported on a left-sided predominance of colorectal cancers in the young (under age 50). Given the predilection of young African Americans for the disease, we wondered if there may be a difference in the biology of colorectal carcinogenesis between this group and Caucasians. Compare the distribution of colorectal cancer in African American patients and Caucasians under age 50, and describe implications for screening in these groups. Colorectal cancer patients diagnosed under the age of 50 between the years 2000 and 2016. All races other than African American and Caucasian and all patients with hereditary colon cancer or inflammatory bowel disease were excluded. race, age at diagnosis (5 subgroups: < 20, 20-29, 30-39, 40-44, and 45-49years) and cancer location; right (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure), left (descending colon and sigmoid colon), or rectal. 759 patients were included; 695 (91.6%) were Caucasian and 64 (8.4%) were African American. Most cases were diagnosed between ages 40 and 49 (African American = 75%, Caucasian = 69.5%). Rectal cancer was most common in both races, although significantly more common in Caucasian than in African American patients (64.2% vs 39.1%). Right colon cancer was more commonly found in African Americans (37.5%) compared with Caucasians (18%) (p = 0.0002). The ratio of rectal to right-sided colon cancer in African Americans was 1:1 compared with 3.6:1 in Caucasians. Relatively low number of African American patients CONCLUSION: The high rate of right-sided cancer in young African American patients means that they should be screened with colonoscopy. The increased incidence of right-sided cancers may represent a different biology of carcinogenesis in African Americans and deserves further study.

Abstract 834: Epigenome-wide profiling of DNA methylation in peripheral blood leukocytes and the prognosis of prostate cancer patients in African Americans

Abstract Introduction: DNA methylation at CpG sites plays important roles in cancer development and progression. Hypermethylation of the promoter regions of tumor suppressor genes leads to gene silencing whereas global hypomethylation may affect chromosome structure and cause genomic instability. African Americans have higher incidence and mortality rates of prostate cancer than other ethnic groups. The goals of this study are to investigate the role of global DNA methylation in prostate cancer aggressiveness and identify CpG site methylations as predictors of aggressive prostate cancer in African Americans. Methods: We measured global DNA methylation level of long interspersed nucleotide elements (LINE-1) and subtelomeric repeat (D4Z4) in leukocyte DNA from ~300 African American prostate cancer patients and compared their methylation levels between different clinicopathological variables at diagnosis. We then analyzed the association of the LINE-1 and D4Z4 methylation with the risk of biochemical recurrence (BCR) using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation.. We also used Illumina’s HumanMethylationEPIC beadchip to profile 850K CpG site methylation in leukocytes and analzyed their associations with prostate cancer aggressiveness. Results: There was no significant differences in the methylation level of LINE-1 between clinically defined aggressive and non-aggressive PCa at diagnosis and LINE-1 methylation was not associated with BCR either. However, the methylation of subtelomeric region D4Z4 was associated with BCR. Patients with higher methylation of D4Z4 exhibited an increased risk of BCR (HR=3.47, 95% CI, 1.10 - 10.97) compared to patients in the lower methylation after adjustment of age, BMI, smoking status, pack year, D’Amico risk groups, and treatments. In Kaplan-Meier survival analysis, patients with higher D4Z4 methylation level had a significantly shorter BCR-free survival time than those with lower methylation level (log rank P = 0.0071). When analyzing individua CpG site methylation, we identified a number of CpG site that can distinguish aggressive from non-aggressive prostate cancer and found a CpG methylation signature that can identify a subgroup of patients with aggressive prostate cancer in African Americans. Conclusions: These data suggest that methylation in the subtelomeric region D4Z4 may be able to predict worse prognosis of patients. Individual CpG site methylation may be promising biomarkers for the identification of aggressive prostate cancer in African Americans. Citation Format: Junfeng Xu, Chia-Wen Tsai, Wen-Shin Chang, Da-Tian Bau, Jian Gu. Epigenome-wide profiling of DNA methylation in peripheral blood leukocytes and the prognosis of prostate cancer patients in African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 834.

Participation of African Americans in clinical trials supporting FDA approval of cancer drugs.

e18135 Background: African Americans comprise 12% of the total United States population. Lifetime probability of developing cancer in African Americans is 37.55%. The 5-year relative survival rate is 68% in Caucasians and 61% in African Americans for all cancers combined. Concerns exist that African Americans are underrepresented in trials of cancer medications. We sought to examine African Americans participation for pivotal cancer medications trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. Methods: On the basis of publicly available FDA reviews, the authors assessed enrollment of African Americans in trials supporting 75 drug approvals from 2014 to 2018. Prevalence-corrected estimates for the participation of African Americans were calculated as the percentage of African Americans among trial participants divided by the percentage of African Americans in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of African Americans in the trial and disease population. Results: A total of 61763 patients enrolled in clinical trials, which resulted in subsequent FDA approval. The proportion of African Americans enrolled in the clinical trials that led to cancer medication approval in the 5-year period was 7.44%. The calculated PPR for participation of African Americans in clinical trials that led to drug approval for all cancers combined was 0.31. The results were consistent across major cancer subtypes including breast cancer (PPR of 0.29), prostate cancer (PPR of 0.18), and lung cancer (PPR of 0.15). Skin cancer, colorectal cancers and hematological malignancies results were also consistent with low PPR. Conclusions: African Americans were under represented in trials of drugs for all cancer types combined. Efforts should be made to increase the proportion of participation of African Americans in clinical trials.

Lung cancer in African-Americans and analysis of estrogen plus progestin use.

e18258 Background: The 15-year Women’s Health Initiative (WHI) sponsored by the NIH has provided a robust dataset on health risks for post-menopausal black women (BW), including the impact of hormone therapy (HRT) on cancer risk. Women enrolled in the WHI randomized, placebo-controlled trial and taking HRT demonstrated no increase in lung cancer incidence, but a statistically significant increase in mortality. However, effects of estrogen plus progestin on non-small cell lung cancer (NSCLC) incidence and outcomes has not been extensively examined, especially in African Ancestry (AA) and smoking history. Methods: Study participants were identified who met WHI clinical trial entry criteria. Cox regression models and Kaplan-Meier method plots were utilized. Analyses adjusted for age, BMI, education, smoking status, alcohol use, health status, and physical activity. A secondary analysis was performed on BW based on AA via Affymetrix Human SNP Array. Results: 161, 808 pts were enrolled from October 1993 to December 1998 (after exclusions total analytic cohort = 142,503). 128,682 (90%) were white (WW) and 13,821 (10%) were BW. BW had lower incidence of NSCLC compared to WW (HR 0.68; P &lt; .0001). HRT participants had a 55% increase in incidence of NSCLC (p &lt; .0001). Former alcohol users had highest risk of NSCLC incidence (HR 2.72; p &lt; 0.0001). Age groups (55-59 years; 60-69 years; 70-79 years) were significantly less associated with BW compared to the youngest(50-54 years; P &lt; .0001). HRT participants were more likely BW (OR 1.17; p &lt; .0001). More current smokers were BW compared to WW (OR 1.75; p &lt; .0001). HRT participants had increased risk of death to NSCLC (HR 1.29; p &lt; .001). There was a trend for survival (p = 0.3667) in WW participants compared to BW (32 vs 28.0 months, respectively). BW who had &gt; 80% AA had a decreased incidence NSCLC trend compared to BW with &lt; 80% AA (HR 0.81; p = 0.2806). Conclusions: BW, especially those with high levels of AA had decreased incidence of NSCLC. Those patients who received HRT had higher incidence and death from NSCLC. Further investigations are required to understand the mechanisms that AA and HRT alter risks associated with NSCLC.