• IBD
• colorectal cancer
• liver transplantation
• oesophageal cancer

• Adenoma
• Cancer
• Colorectal
• Quality
• Screening

• Adenoma
• Colonic polyps
• Distribution

• Adenoma/pathology
• Adult
• Aged
• Colonic Polyps/pathology
• Colonoscopy
• Colorectal Neoplasms/pathology
• Female
• Humans
• Intestinal Polyps/pathology
• Male
• Middle Aged
• Rectal Diseases/pathology
• Republic of Korea
• Retrospective Studies
• Time Factors

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.

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.

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.

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.

• African Americans
• Colon adenoma
• GPNMB

• advanced adenoma
• colonic adenoma
• colonic polyps
• colonoscopy
• epidemiology

• African Americans
• colorectal cancer
• metabolomics
• metagenomic linkage groups
• microbiota

• G12 MD007597 NIMHD NIH HHS
• KL2 TR001432 NCATS NIH HHS
• UL1 TR000101 NCATS NIH HHS
• UL1 TR001409 NCATS NIH HHS

• Endoscopic mucosal resection
• antibiotics
• colon polyps

• Anti-Bacterial Agents
• Colonic Polyps
• Colonoscopy
• Endoscopic Mucosal Resection
• Humans
• Postoperative Complications

• Advanced Adenoma
• Colorectal Polyp
• Diminutive and Small

• Adenoma/epidemiology
• Adenoma/metabolism
• Adenoma/pathology
• Adult
• Age Factors
• Aged
• Colonic Neoplasms/epidemiology
• Colonic Neoplasms/metabolism
• Colonic Neoplasms/pathology
• Colonic Polyps/pathology
• Colonoscopy
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Retrospective Studies
• Risk Factors
• Sex Factors

• Yeungnam University

Colorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients.

Patients’ tissue samples (n = 143) have been arranged on three tissue microarrays for normal (n = 26), adenoma (n = 68) and cancer (n = 49) samples. Immunohistochemistry was used to detect MACC1 expression. Blood samples (n = 93) from normal (n = 45), hyperplastic (n = 15) and tubular adenoma (n = 33) patients were used to assess MACC1 transcripts using qRT-PCR. Distribution of continuous variables was tested between different diagnoses with Kruskal–Wallis test. Categorical variables were tested by Chi square test. We assessed the prognostic ability of IHC staining by calculating area under receiver operating characteristics curve (ROC) for adenoma and cancer separately. Differences between groups in terms of MACC1 transcript levels in plasma were calculated by using non-parametric (exact) Wilcoxon-Mann–Whitney tests. We performed all calculations with SPSS, version 21.

In patient tissues, there was a statistically significant difference in MACC1 expression in normal vs. adenoma samples (p = 0.004) and normal vs. cancer samples (p < 0.001). There was however no major difference in MACC1 expression between adenoma vs. cancer cases or tubular adenomas vs tubulovillous adenomas. The area under the curve for both normal vs. adenoma and normal vs. cancer cases were 70 and 67 %, respectively. MACC1 expression was not correlated to age, gender or anatomical sample location. In patient plasma, MACC1 transcripts in adenoma patients were significantly higher than in plasma from normal patients (p = 0.014). However, the difference between normal and hyperplastic plasma MACC1 transcripts was not statistically significant.

Metastasis-associated in colon cancer 1 is expressed at early stages of colorectal oncogenesis within the affected colonic tissue in this patient cohort. The plasma transcripts can be used to stratify African American patients at risk for potential malignant colonic lesions.

• Adenoma
• Colorectal cancer
• MACC1
• Prognosis

• Colonic Neoplasms/diagnosis
• Healthcare Disparities
• Humans
• Mass Screening
• North Carolina

• T32 DK007568 NIDDK NIH HHS

Uninsured individuals have lower rates of screening colonoscopy (SC), and little is known regarding the pathology results obtained when they undergo colonoscopies. Since 2004, we have participated in a program that offers SC to uninsured New Yorkers; herein, we report our findings.

Uninsured, average-risk patients who were at least 50 years of age underwent SC at our institution between April 2004 and June 2011. We analyzed polyp pathology, location, size, incidence of adenomas, and incidence of adenomas with advanced pathology (AAP) with respect to ethnicity, gender, and age.

Out of 493 referrals, 222 patients completed the colonoscopies. Polyps were identified in 21.2% of all patients; 14% had adenomas, and 4.5% had AAP. The rates of adenomas among African-Americans, Hispanics, and Whites were 24.3%, 12.1%, and 11.6%, respectively, and the corresponding rates of AAP were 10.8%, 3.5%, and 2.3%. Differences in the polyp type, location, and AAP did not reach statistical significance with respect to ethnicity or gender. Patients aged 60 and older were found to have a higher rate of advanced adenomas compared with younger patients (8.6% vs 2.6%, p=0.047).

Further efforts to fund screening colonoscopies for uninsured individuals will likely result in the identification of advanced lesions of the colon before they progress to colorectal cancer.

• Adenoma
• Colonoscopy
• Medically uninsured
• Minorities
• Patient navigator

AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population.

METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ² statistics and t-test.

RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps.

CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

• Colon
• Rectum
• Adenoma
• Carcinoma
• Hispanics

• Adenomatous Polyps/ethnology
• Adenomatous Polyps/pathology
• Carcinoma/ethnology
• Carcinoma/pathology
• Chi-Square Distribution
• Colonic Polyps/ethnology
• Colonic Polyps/pathology
• Colonoscopy
• Colorectal Neoplasms/ethnology
• Colorectal Neoplasms/pathology
• District of Columbia/epidemiology
• Female
• Hispanic or Latino
• Hospitals, University
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Precancerous Conditions/ethnology
• Precancerous Conditions/pathology
• Prevalence
• Retrospective Studies
• Time Factors
• Urban Health

• Acromegaly/blood
• Acromegaly/diagnosis
• Acromegaly/epidemiology
• Adenocarcinoma/diagnosis
• Adenocarcinoma/epidemiology
• Adenomatous Polyps/diagnosis
• Adenomatous Polyps/epidemiology
• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Biomarkers/blood
• Chi-Square Distribution
• Colonic Polyps/diagnosis
• Colonic Polyps/epidemiology
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Cross-Sectional Studies
• Female
• Hospitals, University
• Human Growth Hormone/blood
• Humans
• Japan/epidemiology
• Male
• Middle Aged
• Odds Ratio
• Prevalence
• Retrospective Studies
• Risk Factors
• Young Adult

• DNA methylation
• colon cancer

• obesity
• colorectal polyp
• african american

• Black or African American
• Body Mass Index
• Colonic Polyps/diagnosis
• Colonic Polyps/epidemiology
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Female
• Humans
• Male
• Middle Aged
• Obesity/epidemiology
• Overweight/epidemiology
• Retrospective Studies
• Risk Factors

• G12 MD007597 NIMHD NIH HHS
• UL1 RR031975 NCRR NIH HHS
• UL1 TR000101 NCATS NIH HHS

Gastric Helicobacter pylori (H. pylori) infection and colorectal polyps are more prevalent in African Americans than in the general population. We aimed to investigate whether gastric H. pylori infection is associated with colorectal polyps in African Americans.

Medical records of African Americans, 40 years and older (n = 1256) who underwent bidirectional gastrointestinal endoscopy on the same day were reviewed. H. pylori status was assessed by immunohistochemistry on gastric specimens. Colorectal polyps were confirmed by histological examination of colorectal biopsies. A subset of serum samples from healthy and polyp-bearing patients (n = 163) were analyzed by ELISA for anti-H. pylori and anti-CagA antibodies. The crude and adjusted effect of H. pylori on the risk of colorectal adenoma and polyp were computed by logistic regression models.

The prevalence of colorectal polyps and adenomas were 456 (36%) and 300 (24%) respectively. Colorectal polyps were more prevalent in gastric H. pylori infected than non-infected subjects [43% vs. 34%; Odds Ratio (OR) (95% CI): 1.5 (1.2-1.9), P = 0.001]. Patients with H. pylori-associated chronic active gastritis were at high risk to have adenomas [Unadjusted OR (95% CI): 1.3 (1.0-1.8); P = 0.04]. There was no difference in histopathology, size, or location of polyps with respect to H. pylori status. Gastric H. pylori infection, age, male gender and high risk clinical presentations were independent risk factors for colorectal polyps. Serological testing also revealed a higher prevalence of H. pylori and its toxin Cag-A in polyp patients vs. non polyp patients’ sera, although in a non-statistically significant manner.

This study showed that current gastric H. pylori infection is associated with an increased risk of colorectal polyps in African Americans. Patients with H. pylori induced gastritis may benefit from early screening colonoscopy as a preventative measure for colorectal cancer.

• African Americans
• RRBS
• colon cancer
• neoplasia

• Black or African American
• Bacteria/classification
• Colonic Polyps/microbiology
• Feces/microbiology
• Humans
• Metagenomics
• Microbiota/genetics
• Oligonucleotide Array Sequence Analysis
• Phylogeny
• Sequence Analysis, DNA

• UL1 RR031975 NCRR NIH HHS
• UL1 TR000101 NCATS NIH HHS
• UL1RR031975 NCRR NIH HHS
• UL1TR000101 NCATS NIH HHS
• G12 MD007597 NIMHD NIH HHS
• G12MD007597 NIMHD NIH HHS

• Black or African American/psychology
• Black or African American/statistics & numerical data
• Attitude to Health/ethnology
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/ethnology
• Colorectal Neoplasms/psychology
• Early Detection of Cancer/psychology
• Female
• Humans
• Male
• Middle Aged
• Patient Compliance
• Patient Education as Topic
• Retrospective Studies
• Sex Factors
• Surveys and Questionnaires
• White People/psychology
• White People/statistics & numerical data

• colonic adenoma
• colon cancer stem cells
• african american
• caucasians
• risk of colorectal cancer
• roc analysis

• Adenoma/blood
• Adenoma/genetics
• Black or African American/genetics
• Aged
• Case-Control Studies
• Colonic Neoplasms/blood
• Colonic Neoplasms/genetics
• Colonic Polyps/blood
• Colonic Polyps/genetics
• DNA Methylation/genetics
• Female
• Genetic Predisposition to Disease
• Humans
• Intercellular Signaling Peptides and Proteins/genetics
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide/genetics
• Promoter Regions, Genetic/genetics
• Receptors, Calcitriol/genetics
• Risk Factors
• Seasons
• Vitamin D/blood

• P30 DK042086 NIDDK NIH HHS
• R01 CA102681 NCI NIH HHS
• Intramural NIH HHS
• P30 DK42086 NIDDK NIH HHS
• CA102681 NCI NIH HHS
• K08 CA142892 NCI NIH HHS

Colon cancer is one of the leading causes of cancer related deaths. Its impact on African Americans (AAs) is higher than in the general population both in the incidence and mortality from the disease. Colon cancer aggressiveness in AAs as well as non-frequent check-ups and follow up in this population have been proposed as ways to explain the observed discrepancies. These facts made the detection of early carcinogenesis markers in this population a priority.

Here, we analyzed 50 colon adenomas from AA patients for both microsatellite instability (MSI) and the methylation status of SLC5A8 gene. This gene's product is involved in the transport of butyrate that has anti-proliferative properties through its effects on histone acetylation and gene expression. A proteomic analysis to check the expressed histones in adenoma and normal tissues was also performed.

The analyzed samples displayed 82% (n = 41) methylation level of SLC5A8 gene in adenomas. The MSI-H (high) adenoma were about 18% (n = 9) while the rest were mostly MSS (microsatellite stable) with few MSI-L (Low). No association was found between SLC5A8 methylation and the MSI status. Also, there was no association between SLC5A8 methylation and the sex and age of the patients. However, there were more right sided adenomas with SLC5A8 methylation than the left sided ones. The proteomic analysis revealed distinct histone expression profiles between normal and adenoma tissues.

SLC5A8 is highly methylated in AA colon adenomas which points to its potential use as a marker for early detection. The MSI rate is similar to that found in colon cancer tumors in AAs. These findings suggest that both processes stem from the same epigenetic and genetic events occurring at an early stage in colon carcinogenesis in AAs.