Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 40(1): 27-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892550

RESUMO

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.


Assuntos
Afro-Americanos/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias da Próstata/etiologia , Fumar/efeitos adversos , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
2.
Dig Dis Sci ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832971

RESUMO

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.

3.
Am J Gastroenterol ; 114(10): 1671-1677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478919

RESUMO

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.

4.
Oncotarget ; 10(27): 2607-2624, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31080553

RESUMO

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.

5.
BMC Gastroenterol ; 19(1): 77, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126232

RESUMO

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.


Assuntos
Afro-Americanos/estatística & dados numéricos , Pólipos do Colo/etnologia , Pólipos do Colo/patologia , Neoplasias Colorretais/etnologia , Disparidades nos Níveis de Saúde , Idoso , Colo Ascendente , Colo Sigmoide , Colo Transverso , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reto , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Nutrients ; 11(5)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027364

RESUMO

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.


Assuntos
Carotenoides/farmacologia , Crocus/química , Gastroenteropatias/prevenção & controle , Extratos Vegetais/farmacologia , Especiarias/análise , Carotenoides/química , Carotenoides/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico
8.
BMC Cancer ; 18(1): 1068, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400781

RESUMO

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.


Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Metilação de DNA/genética , Glicoproteínas de Membrana/genética , Adenoma/diagnóstico , Adenoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Ilhas de CpG/genética , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
9.
Cureus ; 10(8): e3160, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30357033

RESUMO

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.

10.
Clin Med Insights Gastroenterol ; 11: 1179552218778627, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795991

RESUMO

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 esophagogastroduodenoscopy, 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 (P = 0.001). Benign and malignant colonic lesions were significantly more present among older patients: 16% vs 6% (P = .005) and 5% vs 0% (P = .008), respectively. Colitis was more prevalent in younger patients (⩽50): 11% vs 2% (P = .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.

11.
Artigo em Inglês | MEDLINE | ID: mdl-29593647

RESUMO

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 < 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; P < 0.001), 1.5 (95% CI = 1.5(1.1-2.0); P = 0.004), and 1.6 (95% CI = 1.3-2.0; P < 0.001), respectively. There was a positive correlation between serum adiponectin and IGF-1 concentrations with age (r = 0.17, P < 0.001 and r = 0.13, P = 0.009), TNF-α, IGF-1, and leptin concentration with body mass index (BMI) (r = 0.44, P < 0.001; r = 0.11, P = 0.03; and r = 0.48, P < 0.001), respectively. Also, there was a negative correlation between adiponectin and leptin concentrations with BMI (r = -0.40, P < 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.

12.
Oncotarget ; 8(59): 99966-99977, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29245953

RESUMO

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 APC, MSH3, and MSH6 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 MSH6 variants were validated and mapped to the MutS-V region near the MSH2 binding site. For MSH3, 4 known variants were validated and were located in exon 10 (3 non-synonymous) and exon 18 (1 synonymous). As for APC, 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 APC genes in African Americans with colorectal lesions. A greater frequency of variants in genes encoding DNA mismatch repair functions and APC likely plays major roles in colorectal cancer initiation and higher incidence of the disease in African Americans.

13.
Genes (Basel) ; 8(11)2017 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-29120399

RESUMO

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.

14.
Gastroenterology ; 153(4): 910-923, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28807841

RESUMO

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.


Assuntos
Grupos de Populações Continentais , Neoplasias do Sistema Digestório/etnologia , Disparidades nos Níveis de Saúde , Estilo de Vida/etnologia , Neoplasias do Sistema Digestório/diagnóstico , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/terapia , Feminino , Humanos , Incidência , Masculino , Prognóstico , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo , Estados Unidos/epidemiologia
15.
Dig Dis Sci ; 62(8): 2159-2165, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28612194

RESUMO

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/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 < 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.


Assuntos
Afro-Americanos/estatística & dados numéricos , Fígado Gorduroso/virologia , Hepacivirus , Hepatite C Crônica/complicações , Cirrose Hepática/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Fígado Gorduroso/patologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fatores Sexuais , Estados Unidos , Adulto Jovem
16.
Sci Rep ; 7: 41920, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28157220

RESUMO

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.


Assuntos
Neoplasias Colorretais/genética , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Estudos de Casos e Controles , Cromossomos Humanos Par 2/genética , Colômbia , Neoplasias Colorretais/etnologia , Feminino , Loci Gênicos , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
17.
Oncotarget ; 8(5): 7852-7866, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28002797

RESUMO

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% TGFßR2A (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.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Exoma , Perfilação da Expressão Gênica/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento Completo do Exoma/métodos , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Biologia Computacional , Bases de Dados Genéticas , Predisposição Genética para Doença , Irã (Geográfico) , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Transcriptoma
18.
Clin Cancer Res ; 23(8): 2061-2070, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27697996

RESUMO

Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r = 0.801-0.934, all P < 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of 0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn + Ch + m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC = 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions: Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer. Clin Cancer Res; 23(8); 2061-70. ©2016 AACR.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/microbiologia , Fezes/microbiologia , Adulto , Idoso , Área Sob a Curva , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
19.
Next Gener Seq Appl ; 3(2)2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27917406

RESUMO

Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes' function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be responsible for this disparity. We here report genome-wide copy number variations, single nucleotide mutations and DNA methylation findings that might be specific to this population.

20.
Gastroenterol Res Pract ; 2016: 2102674, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27688749

RESUMO

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, and NEFM with 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/ß-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.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA