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Background Up to 30% of colorectal cancers develop through the serrated pathway. African Americans (AAs) suffer a disproportionate burden of colorectal cancer. The aim of this study was to evaluate clinicopathological features of AA patients diagnosed with sessile serrated polyps (SSPs). Methods We conducted a retrospective study of all colonoscopies (n = 12,085) performed at Howard University Hospital, from January 1st, 2010 to December 31st, 2015, of which 83% were in AA patients, (n = 10,027). Among AAs, pathology reports confirmed 4070 patients with polyps including 252 with SSPs. Demographic and clinical variables (i.e. sex, age, BMI, anatomic location, clinical symptoms, polyp size, and clinical indications were collected at colonoscopy. Results In the AA population, the median age was 56 with interquartile range (IQR) of 51 to 62 years, 54% were female, and 48% had a BMI > 30. The most common reason for colonoscopy was screening (53%), whereas the prevalent reasons for diagnostic colonoscopies were changes in bowel habits (18%) and gastrointestinal bleeding (17%). The total number of SSPs among the 252 AA (diagnosed with SSPs) was 338. Of these, 9% (n = 29/338) had some degree of cytological dysplasia, primarily in the ascending colon (n = 6/42, 14%), Transverse colon (n = 2/16, 13%) and rectosigmoid (n = 19/233, 8%). About 24% of patients had more than 2 polyps. Most patients (76%) had distal SSPs (rectal and rectosigmoid), in comparison to 14% of proximal polyps and 10% of bilateral locations. Median SSA/P size for all locations was 0.6 cm. Conclusion The prevalence of SSPs accounts for 6% of all polyps in AA patients and was diagnosed in 2.5% of all colonoscopies (n = 252/10,027), which is higher than Caucasians in the US. SSPs were predominantly located in the left side, as compared to published literature showing the predominance in the right side of the colon. Screening of CRC will have the chance to detect high risk SSA/P in this population.

// Hassan Ashktorab 1 , Hamed Azimi 1 , Sudhir Varma 3 , Edward L. Lee 2 , Adeyinka O. Laiyemo 1 , Michael L. Nickerson 4 and Hassan Brim 2 1 Department of Medicine, Cancer Center, Howard University, Washington, DC, USA 2 Department of Pathology, Howard University College of Medicine, Washington, DC, USA 3 Hithru Analytics, LLC, Silver Spring, MD, USA 4 Laboratory of Translational Genomics, National Cancer Institute, Bethesda, MD, USA Correspondence to: Hassan Ashktorab, email: hashktorab@howard.edu Keywords: colon; targeted sequencing; African Americans; actionable; druggable Received: August 28, 2018 Accepted: January 31, 2019 Published: April 05, 2019 ABSTRACT Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. African Americans are disproportionately affected by CRC. Our hypothesis is that driver genes with known and novel mutations have an impact on CRC outcome in this population. Therefore, we investigated the variants’ profiles in a panel of 15 CRC genes. Patients & Methods: Colorectal specimens (n=140) were analyzed by targeted exome sequencing using an Ion Torrent platform. Detected variants were validated in 36 samples by Illumina sequencing. The novel status of the validated variants was determined by comparison to publicly available databases. Annotated using ANNOVAR and in-silico functional analysis of these variants were performed to determine likely pathogenic variants. Results: Overall, 121 known and novel variants were validated: APC (27%), AMER1 (3%) , ARID1 (7%), MSH3 (12%), MSH6 (10%), BRAF (4%), KRAS (6%), FBXW7 (4%), PIK3CA (6%), SMAD4 (5%), SOX9 (2%), TCF7L2 (2%), TGFBR2 (5%), TP53 (7%). From these validated variants, 12% were novel in 8 genes (AMER1, APC, ARID1A, BRAF, MSH6, PIK3CA, SMAD4, and TCF7L2 ). Of the validated variants, 23% were non-synonymous, 14% were stopgains, 24% were synonymous and 39% were intronic variants. Conclusion: We here report the specifics of variants’ profiles of African Americans with colorectal lesions. Validated variants showed that Tumor Suppressor Genes (TSGs) APC and ARID1 and DNA Mismatch repair (MMR) genes MSH3 and MSH6 are the genes with the highest numbers of validated variants. Oncogenes KRAS and PIK3CA are also altered and likely participate in the increased proliferative potential of the mutated colonic epithelial cells in this population.

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country.Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed.Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality. Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts.Conclusion: Nearly, 10.5%–53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.

Objective: It is not known whether patients’ ratings of the quality of healthcare services they receive truly correlate with the quality of care from their providers. Understanding this association can potentiate improvement in healthcare delivery. We evaluated the association between patients’ ratings of the quality of healthcare services received and uptake of colorectal cancer (CRC) screening. Subjects and Methods: We used 2 iterations of the Health Information National Trends Survey (HINTS) of adults in the USA. HINTS 2007 (4,007 respondents; weighted population = 75,397,128) evaluated whether respondents were up to date with CRC screening while HINTS 4 cycle 3 (1,562 respondents; weighted population = 76,628,000) evaluated whether participants had ever received CRC screening in the past. All included respondents from both surveys were at least 50 years of age, had no history of CRC, and had rated the quality of healthcare services that they had received at their healthcare provider’s office in the previous 12 months. Results: HINTS 2007 data showed that respondents who rated their healthcare as good or fair/poor were significantly less likely to be up to date with CRC screening compared to those who rated their healthcare as excellent. We found comparable results from analysis of HINTS 4 cycle 3 data with poorer uptake of CRC screening as the healthcare quality ratings of respondents reduced. Conclusion: Our study suggests that patients who reported receiving lower quality of healthcare services were less likely to have undergone and be compliant with CRC screening recommendations. It is important to pay close attention to patient feedback surveys in order to improve healthcare delivery.

A cross-section correlational study was conducted to evaluate the overall quality of life in young adults (AYAs) diagnosed with cancer, and the impact of health-related and non-health-related factors on their quality of life. Fifty-six AYA cancer survivors were recruited to elicit the impact of biological function (cancer type and comorbidity), symptoms, functional status, general perception of health status, gender, and characteristics of the environment on quality of life. Participants experienced higher than average quality of life. Symptoms, functional status, and general perception of health status were significant predictors of quality of life in this group of AYAs diagnosed with cancer. In delivering quality cancer care, nurses must be able to thoroughly assess symptom status, AYA cancer survivors’ perception of their health status, and functioning in order to implement supportive measures to help improve their quality of life.

Background Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential. Aim To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC). Methods We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed. Results Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn’s disease patients (27% vs. 5%, P Conclusion Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.

Chronic hepatitis C virus (HCV) infection disproportionately affects African-Americans (AAs) and is a major contributor to liver failure and mortality. Genetic factors may not be the only cause in outcome disparity. We retrospectively investigated whether genetic host factors, viral genotypes, and treatment compliance in AA patients impacted the efficacy and the sustained virological response (SVR) rate of the interferon (IFN)-based treatment regimen. The medical chart review included 76 African-American patients (age ranging from 26 to 76) with varying levels of hepatitis condition. Fifty-seven (75%) of them had a clinically verifiable HCV infection and were followed by a hepatologist for 2 years at Howard University Hospital in Washington, DC. Both comprehensive metabolic profile and complete blood count analyses were performed. Among the 57 patients whose viral and IL28B genotypes were determined, sixty-eight percent (68%) were infected with viral genotype 1 and 71% harbored the CT allele of the IL28B gene. Among the 12 patients who completed treatment with IFN-based dual or triple therapy, 58% had achieved SVR 12 weeks following completion of treatment; 33% had a partial response with under 6000 viral count after 16 weeks of treatment; and there was one patient with viral genotype 1a and CT allele who did not respond to the medications. The results of this study prove that the PEG IFN-based regimen was effective in treating HCV-infected AA patients despite the current availability of new direct-acting antivirals. The major obstacles contributing to a low reduction in HCV infection and outcome in the AA community were avoidance or lack of treatment or compliance; contraindications, medication side effects, non-adherence, and payer eligibility restrictions.

Background and study aims Negative experiences with bowel preparation are a barrier to uptake of colonoscopy. The aim of this study was to examine the impact of different flavoring of polyethylene glycol (PEG) laxatives on patient satisfaction with and adequacy of bowel preparation during colonoscopy. Patients and methods This was a single-blind (endoscopist), parallel design, randomized trial (NCT 02062112) during which patients scheduled for colonoscopy were assigned to one of three groups: Group 1 (no laxative flavoring, n = 84); Group 2 (flavored entire laxative, n = 90) and Group 3 (tasted PEG with and without flavoring and decided how they want to drink the rest of the laxatives (choice group), n = 82). Patients rated their bowel preparation experience (satisfaction) and endoscopists accessed adequacy of bowel preparation during colonoscopy. Results There were no differences in patient ratings across the groups (1, 2 and 3) in taste of the laxatives (P = 0.67), ease of drinking (P = 0.53), and overall experience of bowel preparation process (P = 0.18). However, higher percentage of patients in the choice group would want the same laxative again if they were going to have a repeat colonoscopy in the future (72.5 % vs 81.3 % vs 88.9 %, P = 0.04). Surprisingly, adequacy of bowel preparation was highest among patients who drank their PEG unflavored (89.3 % vs 80 % vs 75.5 %, P = 0.07) and the had highest rates of adenoma detection (40.5 % vs 23.3 vs 39.0, P = 0.03). Conclusions There were no differences in overall tolerability of bowel preparation by patterns of flavoring of PEG. Those who drank unflavored PEG were less satisfied but had better clinical outcome, suggesting minimum justification effect in bowel preparation process.

Several factors involved in the development of liver fibrosis in African-American patients with chronic hepatitis C have not been well studied. We aimed to evaluate some of these risk factors. We reviewed pathology and medical records of 603 African-Americans with chronic hepatitis C virus (HCV) infection at Howard University Hospital from January 2004 to December 2013. Among the clinical and pathological data collected were HIV (human immunodeficiency virus), HCV genotype, hepatitis B virus (HBV), diabetes mellitus (DM), hypertension (HTN), body mass index (BMI), and hepatic steatosis. The frequency of DM, HTN, HIV, and HBV was 22, 16, 11, and 4%, respectively. Median BMI was 27.3 kg/m2. The frequency of fibrosis stages 0, 1, 2, 3, and 4 was 2, 48, 28, 11, and 11%, respectively. In multivariate logistic regression, we found a significant association between liver fibrosis stage (3–4 vs. 0–2) and HIV infection (OR 2.4, P = 0.026), HTN (OR 3.0, P = 0.001), age (OR 2.6 for every 10 years, P

BACKGROUND: Colorectal and endometrial lesions increase with age. It is not known if these two precursor lesions in sporadic cases associate with each other AIM: To determine the association between colorectal polyps and endometrial polyps (EP) in African Americans (AA). METHODS: We reviewed records of patients referred to gynecology clinics and had colonoscopy at Howard University Hospital from January 2004 to December 2015. We defined cases as all patients who had EP and underwent colonoscopy. For controls, we used EP-free patients who underwent colonoscopy. Logistic regression analysis was used to assess the association between colon polyps and EP. RESULTS: The median age was 60 years in 118 Cases and 57 years in 664 Controls. The overall colorectal polyps prevalence in the two groups was not statistically different (54% in controls vs. 52% in cases, P=0.60). Sessile serrated adenoma/polyps (SSPs) were more frequent in cases (8% vs. 2% in controls, P=0.003). Sigmoid and rectal locations were more prevalent in controls than cases. In multivariate analysis and after adjusting for age, diabetes mellitus (DM) and BMI, SSPs associated with EP occurrence with an Odds Ratio of 4.6 (CI 1.2–16.7, P=0.022). CONCLUSION: Colorectal polyp prevalence was similar in EP patients compared to EP-free controls. However, we observed a significant association between higher-risk SSPs in patients with EP. The prevalence of smoking and DM was higher in these patients. Females with EP might benefit from a screening for colonic lesions in an age-independent manner.

Objectives Patient navigation improves colorectal cancer screening among underserved populations, but limited resources preclude widespread adoption in minority-serving institutions. We evaluated whether a patient's self-selected social contact person can effectively facilitate outpatient screening colonoscopy. Methods From September 2014 to March 2017 in an urban tertiary center, 399 black participants scheduled for outpatient screening colonoscopy self-selected a social contact person to be a facilitator and provided the person's phone number. Of these, 201 participants (50.4%) were randomly assigned to the intervention arm for their social contact persons to be engaged by phone. The study was explained to the social contact person with details about colonoscopy screening and bowel preparation process. The social contacts were asked to assist the participants, provide support, and encourage compliance with the procedures. The social contact person was not contacted in the usual care arm, n = 198 (49.6%). We evaluated attendance to the scheduled outpatient colonoscopy and adequacy of bowel preparation. Analysis was performed by intention to treat. Results The social contact person was reached and agreed to be involved for 130 of the 201 participants (64.7%). No differences were found in the proportion of participants who underwent screening colonoscopy (77.3% vs 77.2%; relative risk = 1.01; 95% confidence interval: 0.91-1.12), but there was a modest increase in the proportion with adequate bowel preparation with social contact involvement (89.1% vs 80.9%; relative risk = 1.10; 95% confidence interval: 1.00-1.21). Discussion Engaging a patient's social network to serve in the role of a patient navigator did not improve compliance to outpatient screening colonoscopy but modestly improved the adequacy of bowel preparation.

Previous studies have suggested an increase in the incidence of colorectal cancer (CRC) in young adults (younger than 50 years). Among older people, African Americans have disproportionally higher CRC incidence and mortality. We assessed whether this CRC disparity also applies to CRC diagnosed among young people. Using the Surveillance, Epidemiology, and End Results cancer registries, a population-based cancer registry covering 25.6 % of the United States’ African American population, we identified patients diagnosed with CRC between the years of 2000–2012. The age-adjusted rates for non-Hispanic whites (NHW), African Americans, and Asian–Pacific Islanders (API) were calculated for the age categories 20–24, 25–29, 30–34, 35–39, and 40–44. CRC age-adjusted incidence is increasing among all three racial groups and was higher for African Americans compared to NHW and API across all years 2000–2012 (P

Background and Aims. Many studies have focused on the determination of methylated targets in colorectal cancer. However, few analyzed the progressive methylation in the sequence from normal to adenoma and ultimately to malignant tumors. This is of utmost importance especially in populations such as African Americans who generally display aggressive tumors at diagnosis and for whom markers of early neoplasia are needed. We aimed to determine methylated targets in the path to colon cancer in African American patients using Reduced Representation Bisulfite Sequencing (RRBS).Methods. Genomic DNA was isolated from fresh frozen tissues of patients with different colon lesions: normal, a tubular adenoma, a tubulovillous adenoma, and five cancers. RRBS was performed on these DNA samples to identify hypermethylation. Alignment, mapping, and confirmed CpG methylation analyses were performed. Preferential hypermethylated pathways were determined using Ingenuity Pathway Analysis (IPA).Results. We identified hypermethylated CpG sites in the following genes:L3MBTL1, NKX6-2, PREX1, TRAF7, PRDM14, andNEFMwith the number of CpG sites being 14, 17, 10, 16, 6, and 6, respectively, after pairwise analysis of normal versus adenoma, adenoma versus cancer, and normal versus cancer. IPA mapped the above-mentioned hypermethylated genes to the Wnt/β-catenin, PI3k/AKT, VEGF, and JAK/STAT3 signaling pathways.Conclusion. This work provides insight into novel differential CpGs hypermethylation sites in colorectal carcinogenesis. Functional analysis of the novel gene targets is needed to confirm their roles in their associated carcinogenic pathways.

Background: Human papillomavirus type 16 (HPV16) is one of the most common and carcinogenic HPV types associated with high risk of anal, vagina, vulva, penis and cervical neoplastic transformations. However, many genetic variants exist within this virus and not all seem to have the same carcinogenic potential. Aim: To determine HPV16 lineages and their association with risk of high-grade anal lesions in African Americans in an inner-city hospital. Methods: We reviewed medical records of 370 African Americans with anal lesions from Jan. 2007 to Dec. 2015. This study was approved by Howard University Institutional Review Board. Demographic, clinical and pathological data including HPV, HIV, HCV (hepatitis C virus), diabetes mellitus, hypertension and body mass index (BMI) were collected. DNA was extracted from a subset of HPV16-positive patients with FFPE tissue samples (72 patients, 111 samples) and used for HPV16 whole-genome sequencing. We assessed HPV16 variant lineages and associations with disease stage. Statistical analyses were performed using Chi-square tests, Student’s t-tests, and logistic regression. Odds ratios (OR) and p-values were calculated for comparisons of normal/condyloma/high-grade dysplasia (HGD) vs. squamous cell carcinoma (SCC) and for normal/condyloma vs. HGD. The most common HPV16 A1 sublineage was used as a reference in these comparisons. Results: Males represented 75% of the patients (n=276), with a median age of 44 years and BMI of 25.8 kg/m2. The frequency of condyloma, high-grade dysplasia, SCC and adenocarcinoma was 191 (52%), 26 (7%), 31 (8%) and 8 (2%), respectively. The frequency of HPV, HIV, and HCV was 231 (68%), 147 (43%) and 42 (12%), respectively. HPV and HIV were risk factors for condyloma and dysplasia (P Citation Format: Hassan Ashktorab, Adeyinka Laiyemo, Lisa Mirabello, Hassan Brim. Anal cancer and its association with HPV16 lineage B in 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-087.

Background: Human papillomavirus type 16 (HPV16) is one of the most common and carcinogenic HPV types associated with high risk of anal, vagina, vulva, penis and cervical neoplastic transformations. However, many genetic variants exist within this virus and not all seem to have the same carcinogenic potential. Aim: To determine HPV16 lineages and their association with risk of high-grade anal lesions in African Americans in an inner-city hospital. Methods: We reviewed medical records of 370 African Americans with anal lesions from Jan. 2007 to Dec. 2015. This study was approved by Howard University Institutional Review Board. Demographic, clinical and pathological data including HPV, HIV, HCV (hepatitis C virus), diabetes mellitus, hypertension and body mass index (BMI) were collected. DNA was extracted from a subset of HPV16-positive patients with FFPE tissue samples (72 patients, 111 samples) and used for HPV16 whole-genome sequencing. We assessed HPV16 variant lineages and associations with disease stage. Statistical analyses were performed using Chi-square tests, Student's t-tests, and logistic regression. Odds ratios (OR) and p-values were calculated for comparisons of normal/condyloma/high-grade dysplasia (HGD) vs. squamous cell carcinoma (SCC) and for normal/condyloma vs. HGD. The most common HPV16 A1 sublineage was used as a reference in these comparisons. Results: Males represented 75% of the patients (n=276), with a median age of 44 years and BMI of 25.8 kg/m2. The frequency of condyloma, high-grade dysplasia, SCC and adenocarcinoma was 191 (52%), 26 (7%), 31 (8%) and 8 (2%), respectively. The frequency of HPV, HIV, and HCV was 231 (68%), 147 (43%) and 42 (12%), respectively. HPV and HIV were risk factors for condyloma and dysplasia (P Conclusion: We show that the majority of patients with anal lesions are young males with HPV and HIV co-infections. HPV16 lineage B was associated with a high risk of SCC development. Citation Format: Hassan Brim, Lisa Mirabello, Ali Afsari, Muneer Abbas, Meredith Yeager, Joseph Boland, Sara Bass, Mia Steinberg, Michael Cullen, Adeyinka Laiyemo, Tammy Naab, Babak Shokrani, Edward Lee, Mehdi Nouraie, Hassan Ashktorab. Anal cancer among African Americans associate with HPV16 lineage B and HIV [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2027.

Colorectal cancer is the third leading cause of cancer-related deaths in the United States, and rates are highest among African Americans (AAs). Sessile serrated adenoma/polyps (SSA/Ps) may be precursors to up to 30% of all colorectal cancers. Flat and mucinous features make SSA/Ps difficult to detect and diagnose. As such, there is a need for specific sensitive molecular biomarkers for an accurate and reliable diagnosis. Our aim was to assess the diagnostic value of molecular biomarkers that may distinguish SSA/Ps from benign hyperplastic polyps (HPs) among AA SSA/P patients. We conducted a retrospective study of all colonoscopies (n=12,085) performed at Howard University Hospital (2010-2015), which confirmed 4,070 AA patients with polyps, including 252 with SSA/Ps. Gene expression and mutation frequency profiles were analyzed in a total of 47 patients (62 specimens: 29 SSA/Ps, 26 HPs, 3 tubular adenomas, and 4 normal tissues). We tested 4 transcripts (MUC6, FSCN1, SEMG1, and TRNP1) using qRT-PCR. MSI and BRAF mutations were analyzed. CIMP analysis was performed using CACNA1G, IGF2, NEUROG1, RUNX, SOCS, and MLH1. In a parallel study, we assessed the association between endometrial polyp occurrence in patients with different types of colorectal lesions. MUC6, SEMG1, TRNP1, and FSCN1 were significantly more expressed in SSA/Ps vs. HPs (P 0.05). There was a higher loss of MLH1 expression in HPs than SSA/Ps (42.9% showing expression vs 70.3% IHC staining >=2 in HPs and SSA/Ps). The SSA/Ps in our AA study were primarily distal (67%). In female patients, SSA/Ps associated with the higher frequency of endometrial polyps (8% vs. 2% in controls, p=0.003). Our results show that MUC6-SEMG1-TRNP1 expression and BRAF mutation have the strongest correlation with SSA/Ps. The distal location might help explain why MSI and CIMP may not be optimal molecular biomarkers in African American patients with SSA/Ps. These markers may be of high relevance for the diagnosis of ambiguous lesions and will benefit patients’ management for scheduling follow-ups based on the nature of index lesions. Females with colon lesions of the SSA/Ps type might benefit from a screening for an endometrial polyp in an age-independent manner. Citation Format: Hassan Ashktorab, Saman Azam, Babak Shokrani, Edward Lee, Taraneh Arjomand, Priyanka Kanth, Don Delker, Adeyinka Laiyemo, John Caretheres, Mehdi Nouraie, Hassan Brim. Molecular characterization of sessile serrated adenoma/polyps: A risk factor for higher colorectal cancer that further associates with endometrial polyps in female 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 IA35.

Background: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS). Methods: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA). Results: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: ELMO3 (Engulfment and cell motility 3), SLC6A2 (Solute carrier family 6 member 2), SYNM (Synemin), and HMX2 (Homeobox 2). The ELMO3 promoter was significantly hypomethylated at five CpG sites, SYNM at two CpG sites, SLC6A2 at one CpG site, and the HMX2 gene at one CpG site. IPA placed these genes within important carcinogenic pathways. Conclusions: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy.

Objective Obesity is one of the risk factors for pancreatic cancer and a prognostic factor for acute-chronic pancreatitis. Aim To explore the relationship and association between obesity and pancreatic cysts over a 25-year period in African American patients. Methods We reviewed the medical records of 207 patients diagnosed with pancreatic cysts via radiology and pathology data from January 1988 to December 2012. A control group was selected from a separate group of healthy patients without a history of pancreatic disease. The patients were evaluated in five groups according to the last 20 years of diagnosis in five-year intervals. Results Most patients with pancreatic cyst (73%) were overweight (defined as a body mass index (BMI) ≥ 25), and 53% had a history of chronic pancreatitis compared to patients in the control group. There was a significant difference between the two groups; 79% of patients group were overweight (BMI ≥ 25) vs. 66% in control group (p = 0.02). The incidence of obese and overweight patients was significant (85%) during the 2008 to 2012 interval for the test group (p = 0.009). Conclusion Given the increasing proportion of obese pancreatic cyst patients in recent decades compared to the proportion noted in the 1990s, obesity plays a large role in the formation of pancreatic cysts.

“Downhill” esophageal varices are formed in upper two-thirds of the esophagus as a consequence of a superior vena cava obstruction. We present a case of 55-year-old African-American female with a medical history of multiple comorbidities, including end-stage renal disease, who presented with an upper gastrointestinal bleed and was found to have distended neck veins on physical examination. She gave a history of the insertion of an intravenous central line in her neck area for hemodialysis purposes about six years previously. An endoscopy showed the presence of esophageal varices and computed tomography (CT) of the abdomen showed the presence of a superior vena cava (SVC) obstruction. The patient was managed supportively. This case represents a rare cause of acute upper gastrointestinal bleeding in an individual with a central line for dialysis leading to SVC thrombosis.

Objective Cancer imposes higher burden on men. Sex differences in healthcare utilization may contribute to this problem. We compared healthcare utilization among adults with and without a history of cancer as measured by having at least one physician visit within the previous 12 months. Material and methods We analyzed data from 7,229 responders (weighted population size=211,722,892) enrolled in the 2007 Health Information and National Trends Survey (HINTS), a nationally representative sample of non-institutionalized adults in the United States. We used survey weights in all analyses and variance estimation procedures to account for the complex survey design and used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Study participants consisted of 2808 (48.6%) males and 4421 (51.4%) females. Overall, men were less likely to have seen a physician within the previous 12 months (OR=0.39; 95% CI: 0.31-0.48) regardless of their cancer status. Cancer survivors were more likely to visit a physician within the previous 12 months (OR=2.01; 95% CI: 1.28-3.19) regardless of sex. When stratified by personal history of cancer, men without a history of cancer were less likely to visit a physician (OR=0.38; 95% CI: 0.30-0.47) whereas men with a history of cancer were as likely to have seen a physician in the previous 12 months as women with similar cancer status (OR=1.24; 95% CI: 0.44-3.45). Conclusion Men increase their healthcare utilization to that of women only after they receive diagnosis of cancer. Targeted interventions to promote utilization of preventive care services by men are needed to reduce the burden of chronic illnesses including cancer among men.

African Americans suffer the highest burden from colorectal cancer (CRC) in the USA. Studies have suggested that healthcare access and poorer utilization of preventive services may be playing more of a role in this disparity. However, African Americans also tend to develop CRC at younger ages and are more likely to have proximal cancers. This raises the possibility of higher genetic predisposition to CRC among African Americans and this has not been well studied. In this article, we reviewed possible genetic basis underpinning biological differences in CRC burden in the USA.

Background Complementary and alternative medicine (CAM) use has been increasing and these unconventional therapies do have important adverse effects. We evaluated predictors of CAM use among U.S. adults. Methods We analyzed the 2007 Health Information National Trends Survey (n = 7503) and used logistic regression models to evaluate the association of demographic, lifestyle characteristics and healthcare perceptions of respondents who used CAM within the previous 12 months (n = 1980) versus those who did not (n = 5523). We used survey weights in all analyses and performed variance estimations using Taylor series linearization to account for the complex survey design. Results Females (odds ratio [OR] = 1.46; 95% confidence interval [CI]: 1.15 − 1.86), college graduates (OR = 1.61; 95% CI: 1.24 − 2.08) and those who considered the quality of their healthcare to be poor (OR = 2.16; 95% CI: 1.28 − 3.65) were more likely to use CAM, whereas blacks (OR = 0.58; 95% CI: 0.39 − 0.85) were less likely to use CAM. Among CAM users, 47.6% did not inform their doctors. However, no factor predicted those who did not inform their doctors of their CAM use. Conclusions Many adults in the United States use CAM without informing their doctors. Care providers should inquire about CAM usage from their patients, document them and counsel their patients regarding their use of these less regulated therapies.

The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha (TNF-α) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed to investigate the blood serum levels of these biomarkers in colorectal adenoma. The case–control study consisted of serum from 180 African American patients with colon adenoma (cases) and 198 healthy African Americans (controls) at Howard University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-α detection and quantification. Statistical analysis was performed by t-test and multivariate logistic regression. The respective differences in median leptin, adiponectin, IGF-1, and TNF-α levels between control and case groups (13.9 vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were statistically significant (P

Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC). To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA) and genomic content (metagenomics). Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR) using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.

Objectives Obesity is associated with the activation of the molecular pathways that increase the risk of colorectal cancer. Increasing body mass index may accelerate the development of adenomatous polyps, the antecedent lesion of colorectal cancer. The aim of this study was to assess the BMI effect on the risk of colonic polyp and adenoma in African-American. Methods The records of 923 patients who underwent colonoscopy were examined. Demographic and clinical data were collected before colonoscopy. Polyp and adenoma diagnosis were confirmed by pathology examinations. Results Overall, 43% of the patients were male, median age was 57 years and 77% had BMI ≥ 25.0 kg/m2. The frequency of colorectal polyps and adenomas were 61 and 35%, respectively. BMI ≥ 25.0 (OR = 1.61, 95% CI = 1.14-2.26), smoking (OR = 1.61, 95% CI = 1.15-2.26) and history of colon polyps (OR = 1.64, 95% CI = 1.09-2.47) were associated with higher risk of colon polyp. BMI ≥ 25.0 (OR = 1.81, 95% CI = 1.24-2.62), age (OR = 1.04, 95% CI = 1.02-2.05 for each year), male gender (OR = 1.38, 95% CI = 1.02-1.86), and smoking (OR = 1.73, 95% CI = 1.23-2.42) were associated with higher risk of colon adenoma. Conclusion Male and overweight African-Americans are at higher risk of colorectal adenoma. The findings of this study could be applied for risk stratification and modifying the colorectal cancer prevention including screening guideline in African Americans.

Background: Colon and endometrial polyps are current health issues and their incidences are on the rise. Due to conflicting reports of higher colon polyps in patients with endometrial polyps, we aimed to evaluate if there is such an association in African Americans, a population at high risk for colorectal cancer. Method: We retrospectively reviewed all female patients who had endometrial (EN) presentations (n=3,600) and colonoscopy (n=14,888) at Howard University Hospital from January 2004 to December 2015. We selected cases with endometrial poly and control without this diagnosis who underwent colonoscopy. Clinical [Body Mass Index (BMI), diabetes (DM), hypertension (HTN), Tamoxifen intake, age] and pathological (histology, location, type of lesions) features of Cases and Controls were collected. Association between EN and colon polyp was tested using multivariable logistic regression analysis. We excluded the patients with endometrial cancer. Results: We recruited 664 cases and 118 controls. Cases were statistically significant older (median age of 60 vs. 57 in controls) and had higher rates of smoking and DM than controls. However, the overall colon polyp prevalence in the two groups was not statistically different (54% vs 52% in controls and cases, respectively). In subgroups of subject with colon polyp, sigmoid and rectal polyps were more prevalent in controls than cases. Sessile serrated polyps/adenomas (SSPs) were more frequent in cases (8% vs. 2%, p=0.03) while benign mucosa was more so in controls. Whether considering the overall study population or just those with colon polyps, SSPs lesions associated with an Odds Ratio of 4.6 (p=0.02) for EN polyp occurrence, after adjusting for confounder. Conclusion: Our study shows that the overall colon polyp’s prevalence was similar in endometrial polyp patients compared to endometrial-polyp free controls. However, a significant association between SSP with endometrial polyps was noted. Females with colon lesions of the SSP type might benefit from a screening for endometrial polyp in an age-independent manner. Note: This abstract was not presented at the meeting. Citation Format: Hassan Brim, Taraneh Tarjoman, Shirin Ganjali, Saman Azam, Negin Farsi, Edward Lee, Babak Shokrani, Farshad Aduli, Carla Williams, Adeyinka Laiyemo, Akbar Soleimani, Zaki Sherif, Mehdi syed Nouraie, Hassan Ashktorab. Colon sessile serrated polyps associate with endometrial polyps [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 4003.