Publications by authors named "Hassan Brim"

81 Publications

Trends in the Incidence of Hepatocellular Carcinoma in Washington DC: A Single Institutional Cohort Study (1959-2013).

J Natl Med Assoc 2021 Feb 26. Epub 2021 Feb 26.

Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA.

The African American (AA) community in Washington DC is at an elevated risk for hepatocellular carcinoma (HCC) that has a dismal prognosis. The recent rapid increase in the incidence and diagnosis of HCC and liver metastases (LM) in DC prompted us to evaluate the past six decades of this incidence and some of its underlying causes using a single institutional cohort in a hospital located in the center of the city. Electronic medical and pathology records of 454 liver cancer patients from 1959 to 2013 at Howard University Hospital (HUH) were reviewed. Demographic, clinical and pathology characteristics were examined, and statistical analysis was performed using Wilcoxon rank-sum test. Incidence of HCC rose substantially between 1959 and 2013, increasing eight-fold from 1.05 to 8.0 per 100,000 AAs. The rate of increase in the last decade was highest at 550%. Cases were disproportionately male (67.2%), and median age at diagnosis was 57 years. Towards the last decade, the most common etiology for HCC was nonalcoholic fatty liver disease (NAFLD) followed by NAFLD/HCV combination. Liver cancer was clustered in the eastern region of DC in wards 4, 5, 7, and 8. Cases of liver metastases clinically diagnosed and confirmed by biopsies increased 96.4% from 1959 to 1968 to 2009-2013. This study confirms that HCC incidence has been increasing (initially driven by HCV, and NAFLD in the latter decades) more rapidly in DC than previously believed, highlighting the impact of case definitions especially regarding NAFLD in the context of changing diagnostic approaches including the revised ICD10. The rising burden, disproportionate population distribution, and low survival rate among AAs emphasize the importance of prevention and early detection as a public health imperative.
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http://dx.doi.org/10.1016/j.jnma.2021.02.001DOI Listing
February 2021

A Comprehensive Analysis of COVID-19 Impact in Latin America.

Res Sq 2021 Jan 8. Epub 2021 Jan 8.

: 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. 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. 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. 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.
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http://dx.doi.org/10.21203/rs.3.rs-141245/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805457PMC
January 2021

COVID-19 in Latin America: Symptoms, Morbidities, and Gastrointestinal Manifestations.

Gastroenterology 2021 02 6;160(3):938-940. Epub 2020 Nov 6.

Department of Medicine, Howard University College of Medicine, Washington, District of Columbia; Department of Pathology and Cancer Center, Howard University College of Medicine, Washington, District of Columbia; Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, District of Columbia.

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http://dx.doi.org/10.1053/j.gastro.2020.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644436PMC
February 2021

Association of Human Papillomavirus Genotype 16 Lineages With Anal Cancer Histologies Among African Americans.

Gastroenterology 2021 Feb 17;160(3):922-924. Epub 2020 Oct 17.

Departments of Internal Medicine, Surgery, and Pathology, Howard University College of Medicine, Washington DC.

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http://dx.doi.org/10.1053/j.gastro.2020.10.022DOI Listing
February 2021

Association of patients' perception of quality of healthcare received and colorectal cancer screening uptake: An analysis of two national surveys in the United States.

Med Princ Pract 2020 Oct 13. Epub 2020 Oct 13.

Objective: It is unknown 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.

Subject And Methods: We used two iterations of the Health Information National Trends Survey (HINTS) of adults in the United States. 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 suggested 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.
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http://dx.doi.org/10.1159/000512233DOI Listing
October 2020

Analysis of β-catenin association with obesity in African Americans with premalignant and malignant colorectal lesions.

BMC Gastroenterol 2020 Aug 18;20(1):274. Epub 2020 Aug 18.

Department of Medicine, Department of Pathology and Cancer Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W, Washington, D.C, 20060, USA.

Background: African Americans (AA) are at high risk for Colorectal Cancer (CRC). Studies report a 30-60% increase in CRC risk with physical inactivity, obesity and metabolic syndrome. Activation of the WNT/β-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence also indicates a role of WNT-CTNNB1 signaling in obesity and metabolic diseases.

Aim: To examine the association between obesity, β-Catenin expression and colonic lesions in African Americans.

Methods: We reviewed the pathology records of 152 colorectal specimens from 2010 to 2012 (46 CRCs, 74 advanced adenomas and 32 normal colon tissues). Tissue Microarrays (TMA) were constructed from these samples. Immunohistochemistry (IHC) for CTNNB1 (β-Catenin; clone β-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0 to 4. BMI, sex, age, location of the lesion and other demographic data were obtained.

Results: Positive nuclear staining in normal, advanced adenoma and CRC was 0, 24 and 41%, respectively (P < 0.001). CRC was asso ciated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI = 1.42-8.15, P = 0.006 for positive nuclear staining) compared to non-CRC samples (Normal or advanced adenoma). Nuclear staining percentage has a fair diagnostic ability for CRC with an AUC of 0.63 (95%CI = 0.55-0.71). Overweight/obese patients (BMI > 25) did not show a significant difference in (p = 0.3) nuclear CTNNB1 staining (17% positive in normal weight vs. 27% positive in overweight/obese). The association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1status in CRC stage III and IV (35% of all CRC) was not different from stage I and II (50% vs. 36%, respectively, P = 0.4).

Conclusion: In our study, advanced adenoma and CRC were associated with activation of β-catenin in physically fit, overweight and obese patients. Thus, obesity and WNT/β-Catenin pathway seem to be independent in African American patients. WNT/β-Catenin signaling pathway has a potential to be used as an effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway needs to be investigated further.
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http://dx.doi.org/10.1186/s12876-020-01412-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433356PMC
August 2020

Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells.

Cells 2020 08 3;9(8). Epub 2020 Aug 3.

Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.

The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron's anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.
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http://dx.doi.org/10.3390/cells9081829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463853PMC
August 2020

Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions.

Therap Adv Gastroenterol 2020 27;13:1756284820905482. Epub 2020 May 27.

Department of Pathology, and Medicine, Howard University, 2041 Georgia Avenue NW, Washington, DC 20059, USA.

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: (Engulfment and cell motility 3), (Solute carrier family 6 member 2), (Synemin), and (Homeobox 2). The promoter was significantly hypomethylated at five CpG sites, at two CpG sites, at one CpG site, and the 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.
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http://dx.doi.org/10.1177/1756284820905482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273615PMC
May 2020

Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients.

BMC Gastroenterol 2020 Jun 5;20(1):170. Epub 2020 Jun 5.

Gastroenterology division, Stanford University, School of Medicine, Palo Alto, California, USA.

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 < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (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 < 0.001) within the IBD group.

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.
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http://dx.doi.org/10.1186/s12876-020-01279-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275388PMC
June 2020

Comparison of patterns of laxative ingestion to improve bowel preparation for colonoscopy: a pilot randomized clinical trial.

Endosc Int Open 2020 May 17;8(5):E617-E622. Epub 2020 Apr 17.

Georgetown-Howard Universities Center for Clinical and Translations Science, Washington, District of Columbia, United States.

 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.  This was a single-blind (endoscopist), parallel design, randomized trial (NCT02062112) 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.  There were no differences in patient ratings across the groups (1, 2 and 3) in taste of the laxatives (  = 0.67), ease of drinking (  = 0.53), and overall experience of bowel preparation process (  = 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 %,  = 0.04). Surprisingly, adequacy of bowel preparation was highest among patients who drank their PEG unflavored (89.3 % vs 80 % vs 75.5 %,  = 0.07) and the had highest rates of adenoma detection (40.5 % vs 23.3 vs 39.0,  = 0.03).  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.
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http://dx.doi.org/10.1055/a-1118-3526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165003PMC
May 2020

Altered ARID1A expression in colorectal cancer.

BMC Cancer 2020 Apr 25;20(1):350. Epub 2020 Apr 25.

Cancer Center and Department of Medicine, Howard University, College of Medicine, 2041 Georgia Avenue, N.W., Washington, D.C., 20060, USA.

Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined.

Aim: To investigate the role of ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC.

Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. We used MSP to evaluate methylation of ARID1A. IHC was used to assess ARID1A protein expression. We also evaluated MSI and EMAST status in 18 paired CRC and adjacent normal tissues. 5AzadC was used to assess effect of DNA demethylation on ARID1A expression. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters.

Results: Among the 18 CRC tumors studied, 7 (38.8%) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines.

Conclusion: ARID1A expression is downregulated in CRC tissues which correlates with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contributes to CRC tumorigenesis. However, there was no significant association between ARID1A loss of expression and clinicopathological characteristics. Future in-vivo analysis is warranted to further establish ARID1A role in colorectal neoplastic transformation.
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http://dx.doi.org/10.1186/s12885-020-6706-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183124PMC
April 2020

Factors influencing treatment outcome in hepatitis C virus minority patients at an inner-city hospital: A STROBE-complaint article.

Medicine (Baltimore) 2020 Apr;99(14):e19505

Department of Medicine, Howard University Hospital.

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.
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http://dx.doi.org/10.1097/MD.0000000000019505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220685PMC
April 2020

Genetic Polymorphisms in IL-10 Promoter Are Associated With Smoking and Prostate Cancer Risk in African Americans.

Anticancer Res 2020 Jan;40(1):27-34

Department of Pathology, Howard University College of Medicine, Washington, DC, U.S.A.

Background/aim: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking.

Materials And Methods: A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data.

Results: rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer.

Conclusion: IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.
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http://dx.doi.org/10.21873/anticanres.13923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731238PMC
January 2020

Elevated Risk for Sessile Serrated Polyps in African Americans with Endometrial Polyps.

Dig Dis Sci 2020 09 12;65(9):2686-2690. Epub 2019 Dec 12.

Pathology Department and Cancer Research Center, Howard University College of Medicine, Washington, DC, USA.

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.

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 were 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.
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http://dx.doi.org/10.1007/s10620-019-05991-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289663PMC
September 2020

Using Patients' Social Network to Improve Compliance to Outpatient Screening Colonoscopy Appointments Among Blacks: A Randomized Clinical Trial.

Am J Gastroenterol 2019 10;114(10):1671-1677

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.14309/ajg.0000000000000387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776677PMC
October 2019

Can the rate and location of sessile serrated polyps be part of colorectal Cancer disparity in African Americans?

BMC Gastroenterol 2019 May 24;19(1):77. Epub 2019 May 24.

Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA.

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.
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http://dx.doi.org/10.1186/s12876-019-0996-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534887PMC
May 2019

Driver genes exome sequencing reveals distinct variants in African Americans with colorectal neoplasia.

Oncotarget 2019 Apr 5;10(27):2607-2624. Epub 2019 Apr 5.

Department of Pathology, Howard University College of Medicine, Washington, DC, USA.

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 functional analysis of these variants were performed to determine likely pathogenic variants.

Results: Overall, 121 known and novel variants were validated: (27%), (3%) (7%), (12%), (10%), (4%), (6%), (4%), (6%), (5%), (2%), (2%), (5%), (7%). From these validated variants, 12% were novel in 8 genes and ). 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) and and DNA Mismatch repair (MMR) genes and are the genes with the highest numbers of validated variants. Oncogenes are also altered and likely participate in the increased proliferative potential of the mutated colonic epithelial cells in this population.
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http://dx.doi.org/10.18632/oncotarget.26721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498998PMC
April 2019

Saffron: The Golden Spice with Therapeutic Properties on Digestive Diseases.

Nutrients 2019 Apr 26;11(5). Epub 2019 Apr 26.

Department of Medicine, Department of Pathology and Cancer Center, Howard University College of Medicine, Washington, DC 20059, USA.

Saffron is a natural compound that has been used for centuries in many parts of the world as a food colorant and additive. It was shown to have the ability to mitigate various disorders through its known anti-inflammatory and anti-oxidant properties. Several studies have shown the effectiveness of saffron in the treatment of various chronic diseases like inflammatory bowel diseases, Alzheimer's, rheumatoid arthritis as well as common malignancies of the colon, stomach, lung, breast, and skin. Modern day drugs generally have unwanted side effects, which led to the current trend to use naturally occurring products with therapeutic properties. In the present review, the objective is to systematically analyze the wealth of information regarding the potential mechanisms of action and the medical use of saffron, the "golden spice", especially in digestive diseases. We summarized saffron influence on microbiome, molecular pathways, and inflammation in gastric, colon, liver cancers, and associated inflammations.
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http://dx.doi.org/10.3390/nu11050943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567082PMC
April 2019

Molecular Characterization of Sessile Serrated Adenoma/Polyps From a Large African American Cohort.

Gastroenterology 2019 08 17;157(2):572-574. Epub 2019 Apr 17.

Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC; Department of Pathology, Howard University College of Medicine, Washington, DC.

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http://dx.doi.org/10.1053/j.gastro.2019.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980432PMC
August 2019

GPNMB methylation: a new marker of potentially carcinogenic colon lesions.

BMC Cancer 2018 Nov 6;18(1):1068. Epub 2018 Nov 6.

Department of Medicine, Department of Pathology and Cancer Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W, Washington, D.C, 20060, USA.

Background: Epigenetic plays an important role in colorectal neoplasia process. There is a need to determine sound biomarkers of colorectal cancer (CRC) progression with clinical and therapeutic implications. Therefore, we aimed to examine the role and methylation status of Glyco Protein Non-Metastatic GPNM B (GPNMB) gene in normal, adenoma and CRC in African American (AA) patients.

Methods: The methylation status of 13 CpG sites (chr7: 23287345-23,287,426) in GPNMB gene's promoter, was analyzed by pyrosequencing in human CRC cell lines (HCT116, SW480, and HT29) and microdissected African American paraffin embedded samples (20 normal, 21 non-advanced adenoma (NA), 48 advanced adenoma (AD), and 20 cancer tissues. GPNMB expression was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMA). Correlations between GPNMB methylation and expression with clinicopathological features were analyzed. GPNMB functional analysis was performed in triplicates using cell proliferation, migration and invasion assays in HCT116 colon cell line after stable transfection with a GPNMB-cDNA expression vector.

Results: GPNMB methylation was lower in normal mucosa compared to CRC samples (1/20 [5%] vs. 18/20 [90%]; P < 0.001). AD also had a significantly higher GPNMB methylation frequency than normal colon samples (42/48 [88%] vs 1/20 [5%]; P < 0.001). GPNMB was more frequently methylated in AD than in matched normal mucosa from three patients (3/3 [100%] vs 1/3 [33.3%]; P < 0.001). The frequency of GPNMB methylation in NA differed significantly from that in the normal mucosa (16/21 [76%] vs 1/20 [5%]; P = 0.008). There was statistically significant correlation of higher methylation at advanced stages and lower methylation at stage 1 CRCs (P < 0.05). In agreement with these findings, GPNMB protein expression decreased in CRC tissues compared with AD and NA colon mucosa (p < 0.05). GPNMB overexpression in HCT116 colon cancer cell line decreased cell proliferation [(24 h, P = 0.02), (48 h, P < 0.001, 72 h, P = 0.007)], invasion (p < 0.05) and migration (p > 0.05) compared to the mock-transfected cells.

Conclusion: Our data indicate a high methylation profile leading to a lower GPNMB expression in adenoma and CRC samples. The functional analysis established GPNMB as a potential tumor suppressor gene. As such, GPNMB might be useful as a biomarker of adenomas with high carcinogenic potential.
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http://dx.doi.org/10.1186/s12885-018-4903-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219212PMC
November 2018

Obesity and Pancreatic Cysts in African American Patients.

Cureus 2018 Aug 20;10(8):e3160. Epub 2018 Aug 20.

Department of Medicine & Cancer Center, Howard University College of Medicine, Washington DC, USA.

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.
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http://dx.doi.org/10.7759/cureus.3160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197533PMC
August 2018

Gastrointestinal Lesions in African American Patients With Iron Deficiency Anemia.

Clin Med Insights Gastroenterol 2018 18;11:1179552218778627. Epub 2018 May 18.

Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA.

Background: Iron deficiency anemia (IDA) is a frequent disorder that is associated with many serious diseases. However, the findings of an evaluation of IDA-associated gastrointestinal disorders are lacking among African American patients.

Aim: To determine the most prevalent gastrointestinal lesions among African American patients with IDA especially in young men.

Methods: We reviewed medical records (n = 422) of patients referred for evaluation of IDA from 2008 to 2012. Iron deficiency anemia was diagnosed using clinical laboratory tests. The results of , colonoscopy, and pathology specimens along with demographic data were abstracted and analyzed using Stata.

Results: The mean age was 61.9 years, and 50.5% were women. In total, 189 patients (45%) had gross gastrointestinal (GI) bleeding. The most frequent diagnoses were gastritis (40%), benign colonic lesions (13%), esophagitis (9%), gastric ulcer (6%), and duodenitis (6%). GI bleeding was significantly more frequent in men ( = 0.001). Benign and malignant colonic lesions were significantly more present among older patients: 16% vs 6% ( = .005) and 5% vs 0% ( = .008), respectively. Colitis was more prevalent in younger patients (⩽50): 11% vs 2% ( = .001). In patients with gross lower GI bleeding, the top diagnoses were gastritis (25%), benign colon tumors (10%), and duodenitis (6%). Colon cancer was diagnosed among 15 patients, and all these patients were older than 50 years of age.

Conclusions: Gastritis and colonic lesions are most common associated lesions with IDA among African Americans. So bidirectional endoscopy is required for unrevealing of the cause of IDA in asymptomatic patients.
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http://dx.doi.org/10.1177/1179552218778627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960842PMC
May 2018

Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.

Front Endocrinol (Lausanne) 2018 12;9:77. Epub 2018 Mar 12.

Pathology Department, College of Medicine, Washington, DC, United States.

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 -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 ( < 0.05). In a multivariate model, the odds ratio for adiponectin, TNF-α, and IGF-1 were 2.0 (95% CI = 1.6-2.5;  < 0.001), 1.5 (95% CI = 1.5(1.1-2.0);  = 0.004), and 1.6 (95% CI = 1.3-2.0;  < 0.001), respectively. There was a positive correlation between serum adiponectin and IGF-1 concentrations with age ( = 0.17,  < 0.001 and  = 0.13,  = 0.009), TNF-α, IGF-1, and leptin concentration with body mass index (BMI) ( = 0.44,  < 0.001;  = 0.11,  = 0.03; and  = 0.48,  < 0.001), respectively. Also, there was a negative correlation between adiponectin and leptin concentrations with BMI ( = -0.40,  < 0.001), respectively. These data support the hypothesis that adiponectin, IGF-1, and TNF-α high levels correlate with higher risk of colon adenoma and can thus be used for colorectal adenomas risk assessment.
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http://dx.doi.org/10.3389/fendo.2018.00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857920PMC
March 2018

Distinctive DNA mismatch repair and APC rare variants in African Americans with colorectal neoplasia.

Oncotarget 2017 Nov 7;8(59):99966-99977. Epub 2017 Oct 7.

Department of Pathology, Howard University College of Medicine, Washington, DC, USA.

Purpose: African Americans have a higher incidence and mortality from colorectal cancer. This disparity might be due, in part, to the type of mutations in driver genes. In this study, we examined alterations specific to , , and genes using targeted exome sequencing to determine distinctive variants in the course of neoplastic transformation.

Experimental Design: A total of 140 African American colon samples (30 normal, 21 adenomas, 33 advanced adenomas and 56 cancers) were used as our discovery set on an Ion Torrent platform. A 36 samples subset was resequenced on an Illumina platform for variants' validation. Bioinformatics analyses were performed and novel validated variants are reported.

Results: Two novel variants were validated and mapped to the MutS-V region near the MSH2 binding site. For 4 known variants were validated and were located in exon 10 (3 non-synonymous) and exon 18 (1 synonymous). As for , 20 variants were validated with 4 novel variants: 3 stopgain and 1 non-synonymous. These variants mapped prior to and on the Armadillo repeats region, to the 15-amino acid repeat region, and to the 20-amino acid repeats region, respectively.

Conclusion: We defined novel variants that target DNA mismatch repair and genes in African Americans with colorectal lesions. A greater frequency of variants in genes encoding DNA mismatch repair functions and likely plays major roles in colorectal cancer initiation and higher incidence of the disease in African Americans.
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http://dx.doi.org/10.18632/oncotarget.21557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725144PMC
November 2017

A Microbiomic Analysis in African Americans with Colonic Lesions Reveals Streptococcus sp.VT162 as a Marker of Neoplastic Transformation.

Genes (Basel) 2017 11 9;8(11). Epub 2017 Nov 9.

Department of Pathology and Department of Medicine, Microbiology and Cancer Center, College of Medicine, Howard University, 2041 Georgia Avenue, Washington, DC 20060, USA.

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 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 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 sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects' stools. sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.
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http://dx.doi.org/10.3390/genes8110314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704227PMC
November 2017

Racial Disparity in Gastrointestinal Cancer Risk.

Gastroenterology 2017 10 12;153(4):910-923. Epub 2017 Aug 12.

Division of Gastroenterology, Department of Internal Medicine, Department of Human Genetics and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan. Electronic address:

Cancer from the gastrointestinal tract and its associated excretory organs will occur in more than 300,000 Americans in 2017, with colorectal cancer responsible for >40% of that burden; there will be more than 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to the incidence and mortality of these cancers exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in non-Hispanic whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among blacks. Liver cancer has been most frequent among Asian/Pacific Islanders, chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas, and colorectum show the highest rates among blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socioeconomic and health care access, treatment, and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biologic and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.
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http://dx.doi.org/10.1053/j.gastro.2017.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623134PMC
October 2017

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C.

Dig Dis Sci 2017 08 13;62(8):2159-2165. Epub 2017 Jun 13.

Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA.

Background And Aim: 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.

Methods: 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.

Results: The frequency of DM, HTN, HIV, and HBV was 22, 16, 11, and 4%, respectively. Median BMI was 27.3 kg/m. 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 < 0.001), weight (OR 1.1 for every 10 lb increase, P = 0.002), and steatosis grade (OR 1.6, P = 0.002). The frequency of liver steatosis was 73%. In an ordinal logistic regression, significant risk factors for steatosis were female gender (OR 1.5, P = 0.034) and inflammation grade (P = 0.001).

Conclusion: This study shows that steatosis is independently associated with fibrosis in African-American patients with HCV infection. Female patients were at higher risk of steatosis.
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http://dx.doi.org/10.1007/s10620-017-4626-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706543PMC
August 2017

IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry.

Sci Rep 2017 02 3;7:41920. Epub 2017 Feb 3.

Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US.

Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31-3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk.
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http://dx.doi.org/10.1038/srep41920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291207PMC
February 2017

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer.

Oncotarget 2017 Jan;8(5):7852-7866

Department of Pathology, Howard University College of Medicine, Washington, DC, USA.

Purpose: Next Generation Sequencing (NGS) is currently used to establish mutational profiles in many multigene diseases such as colorectal cancer (CRC), which is on the rise in many parts of the developing World including, Iran. Little is known about its genetic hallmarks in these populations.

Aim: To identify variants in 15 CRC-associated genes in patients of Iranian descent.

Results: There were 51 validated variants distributed on 12 genes: 22% MSH3 (n = 11/51), 10% MSH6 (n = 5/51), 8% AMER1 (n = 4/51), 20% APC (n = 10/51), 2% BRAF (n = 1/51), 2% KRAS (n = 1/51), 12% PIK3CA (n = 6/51), 8% TGFβR2A (n = 4/51), 2% SMAD4 (n = 1/51), 4% SOX9 (n = 2/51), 6% TCF7L2 (n = 3/51), and 6% TP53 (n = 3/51). Most known and distinct variants were in mismatch repair genes (MMR, 32%) and APC (20%). Among oncogenes, PIK3CA was the top target (12%).

Materials And Methods: CRC specimens from 63 Shirazi patients were used to establish the variant' profile on an Ion Torrent platform by targeted exome sequencing. To rule-out technical artifacts, the variants were validated in 13 of these samples using an Illumina NGS platform. Validated variants were annotated and compared to variants from publically available databases. An in-silico functional analysis was performed. MSI status of the analyzed samples was established.

Conclusion: These results illustrate for the first time CRC mutational profile in Iranian patients. MSH3, MSH6, APC and PIK3CA genes seem to play a bigger role in the path to cancer in this population. These findings will potentially lead to informed genetic diagnosis protocol and targeted therapeutic strategies.
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http://dx.doi.org/10.18632/oncotarget.13977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341754PMC
January 2017