• African American
• Disparities
• Gastrointestinal cancers
• Mortality
• Tumor biomarkers

• Humans
• Proto-Oncogene Proteins B-raf/genetics
• Proto-Oncogene Proteins p21(ras)/genetics
• Racial Groups
• Colorectal Neoplasms/pathology
• Mutation
• Microsatellite Instability
• Biomarkers
• Tumor Microenvironment

• R00 CA207848 NCI NIH HHS
• R01 CA255318 NCI NIH HHS

• Butterfly vertebrae
• Congenital scoliosis
• Hemivertebra
• Klippel–Feil syndrome
• Neural tube defects
• Spondylocostal dysostosis
• Vertebral defects

• Humans
• Spine/abnormalities
• Spine/pathology
• Abnormalities, Multiple/pathology
• Klippel-Feil Syndrome/pathology
• Scoliosis
• Hernia, Diaphragmatic/pathology

• 2020/37/B/NZ5/03693 Narodowe Centrum Nauki

• colorectal neoplasms
• genetics
• molecular biology

• Humans
• Female
• Triple Negative Breast Neoplasms/genetics
• Transcriptome
• Black or African American/genetics
• Biology

• U54 CA118623 NCI NIH HHS
• L60 MD002419 NIMHD NIH HHS
• 5U54CA118948 National Cancer Institute (NCI)
• U54-MD007585-26 National Institute on Minority Health and Health Disparities (NIMHD)
• U54 MD007585 NIMHD NIH HHS
• SC1 GM136521 NIGMS NIH HHS
• R01 CA259396-01 National Cancer Institute (NCI)
• R01 CA259396 NCI NIH HHS
• Susan G. Komen (SGK)
• U.S. Department of Defense (DOD)

A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (< 50 years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological features in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease.

A retrospective cohort (2011–2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted.

IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association.

This study revealed distinct histopathological features for LCC, and suggests BAT25 and BAT26 as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

• African
• BAT25
• BAT26
• Colorectal cancer
• Low level microsatellite instability
• Microsatellite stable

Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of “the hallmarks of cancer”, and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites. This condition causes increased systemic inflammation, immune dysregulation, gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis. Periodontal-associated bacteria such as Fusobacterium, Prevotella, Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients. Therefore, a deeper understanding of the association between oral and gastrointestinal bacterial profile, in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race, may play a pivotal role in predicting incidence, prognosis, and lead to the development of new treatments.

• Colorectal cancer
• Oral microbiome
• Gut microbiome
• Hallmarks of cancer
• Racial/ethnic microbial diversity

• Black or African American/genetics
• Aged
• Colonic Neoplasms/diagnosis
• Colonic Neoplasms/ethnology
• Colonic Neoplasms/genetics
• Colonoscopy
• Female
• Genomics/methods
• Healthcare Disparities
• Humans
• Incidence
• Male
• Middle Aged
• Neoplasm Grading
• RNA, Neoplasm/genetics
• Retrospective Studies
• Sequence Analysis, RNA
• Survival Rate/trends
• Tertiary Care Centers
• United States/epidemiology

• R01 CA204806 NCI NIH HHS
• SC1 GM127256 NIGMS NIH HHS

• Cancer
• GPI
• LDHA
• LDHB
• Warburg effect
• genes
• metabolism

• CRISPR-Cas Systems/genetics
• Cell Line, Tumor
• Cell Survival
• Cytokines/genetics
• Cytokines/metabolism
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Knockout Techniques
• Glucose/metabolism
• Glucose-6-Phosphate Isomerase/genetics
• Glucose-6-Phosphate Isomerase/metabolism
• Humans
• Isoenzymes/antagonists & inhibitors
• Isoenzymes/genetics
• Isoenzymes/metabolism
• L-Lactate Dehydrogenase/antagonists & inhibitors
• L-Lactate Dehydrogenase/genetics
• L-Lactate Dehydrogenase/metabolism
• Lactic Acid/metabolism
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Oligonucleotide Array Sequence Analysis
• Warburg Effect, Oncologic

• G12 MD007582 NIMHD NIH HHS
• U54 MD007582 NIMHD NIH HHS

• African American colorectal cancer
• The Cancer Genome Atlas
• copy number variation
• copy-neutral loss of heterozygosity
• genotype and microarray data

Colorectal cancer (CRC) is the fifth leading cause of cancer-related death in China. The incidence of Chinese CRC has increased dramatically with the changes of dietary and lifestyle. However, the genetic landscape of Chinese colorectal cancer mutation is still poorly understood. In this study, we have performed whole exome-sequencing analysis of 63 CRC cases. We found that Chinese CRC were hypermutated, which were enriched in ECM-receptor interaction, antigen processing and presentation, and focal adhesion. Analysis with clinical characteristics indicated that the deficiency of CRC driver gene, FCGBP and NBPF1 conferred CRC development and was showed worse survival rates, which could be the novel regulators and, diagnostic and prognostic biomarkers for Chinese CRC. Taken together, the application of whole exome-sequencing unveiled previously unsuspected somatic mutation landscape in Chinese CRCs, which may expand the understanding of disease mechanisms and provide an alternative personalized treatment for Chinese CRC patients.

• Colorectal cancer
• FCGBP
• NBPF1
• Whole exome-sequencing

• colorectal adenoma
• early-stage colorectal adenocarcinoma
• screen marker
• somatic mutation

• P20 GM125503 NIGMS NIH HHS
• 002.07.09 HRH princess Chulabhorn College

• African Americans
• actionable
• colon
• druggable
• targeted sequencing

• G12 MD007597 NIMHD NIH HHS
• U54 MD007597 NIMHD NIH HHS

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease which primarily manifested with developing adenomas or polyps in colon or rectum. It is caused by the germline mutations in adenomatous polyposis coli (APC) gene. Patients with FAP are usually manifested with “hundreds or even thousands” adenomas or polyps in colon or rectum. However, without proper clinical diagnosis and timely surgical interventions, colorectal adenomas, or polyps gradually increase in size and in numbers which finally leads to colorectal cancer (CRC) at the mean age of 36 years of the patient.

In this study, we identified a family with FAP. In this family, FAP has been diagnosed clinically based on symptoms, medical test reports, and positive family history for three generations. In order to unveil the molecular genetic consequences underlying the disease phenotype, we performed next‐generation sequencing with a customized and designed panel of genes reported to be associated with hereditary CRC. The variant identified by next‐generation sequencing has been validated by Sanger sequencing.

A heterozygous novel insertion [c.3992_3993insA; p.Thr1332Asnfs*10] in exon 16 of APC gene has been identified. This novel insertion is cosegregated well with the FAP phenotype among all the affected members of this family. This mutation causes a frameshift by the formation of a premature stop codon which finally results in the formation of a truncated APC protein of 1,342 amino acids instead of the wild type APC protein of 2,843 amino acids. Hence, this is a loss‐of‐function mutation. This mutation was not found in unaffected family members or in normal control individuals.

Our present study emphasizes the importance of a novel approach of the gene panel‐based high‐throughput sequencing technology for easy and rapid screening for patients with FAP or CRC which will help the clinician for follow‐up and management.

• APC gene
• Chinese population
• colorectal cancer
• familial adenomatous polyposis
• single nucleotide deletion
• targeted next-generation sequencing

• cancer
• genomics
• global health
• global surgery
• low-income
• oncology
• precision medicine
• surgery

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.

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

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%).

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.

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.

• Caucasian
• Iranian
• Shirazi
• colon
• targeted exome sequencing

• African Americans
• colon
• targeted exome sequencing

• G12 MD007597 NIMHD NIH HHS

• African American
• Anal Cancer
• Cancer Disparity
• Cancer Epidemiology
• Cancer Risk
• Colorectal Cancer
• Esophageal Cancer
• Gastric Cancer
• Hepatocellular Carcinoma
• Pancreatic Cancer
• Racial Disparity
• Small Bowel Cancer

• Digestive System Neoplasms/diagnosis
• Digestive System Neoplasms/ethnology
• Digestive System Neoplasms/mortality
• Digestive System Neoplasms/therapy
• Female
• Health Status Disparities
• Humans
• Incidence
• Life Style/ethnology
• Male
• Prognosis
• Racial Groups
• Risk Assessment
• Risk Factors
• Sex Distribution
• Time Factors
• United States/epidemiology

• R01 DK067287 NIDDK NIH HHS
• G12 MD007597 NIMHD NIH HHS
• K08 CA142892 NCI NIH HHS
• R01 CA206010 NCI NIH HHS
• U54 MD007597 NIMHD NIH HHS
• U01 CA162147 NCI NIH HHS

Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes’ B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq^TM Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes’ B (n = 10) and Dukes’ C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes’ B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes’ B and C). In addition, TP53 was more frequently altered in Dukes’ C (n = 7) compared to Dukes’ B (n = 4). Ten variants in APC, namely p.R283^∗, p.N778fs, p.R805^∗, p.Y935fs, p.E941fs, p.E1057^∗, p.I1401fs, p.Q1378^∗, p.E1379^∗, and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.

• APC
• Ion Ampliseq Comprehensive Cancer Panel
• SYNE1
• colorectal cancer
• next generation sequencing
• precision medicine

Over the past two decades there has been remarkable progress in cancer diagnosis, treatment and screening. The basic mechanisms leading to pathogenesis of various types of cancers are also understood better and some patients, if diagnosed at a particular stage go on to lead a normal pre-diagnosis life. Despite these achievements, racial disparity in some cancers remains a mystery. The higher incidence, aggressiveness and mortality of breast, prostate and colorectal cancers (CRCs) in African-Americans as compared to Caucasian-Americans are now well documented. The polyp-carcinoma sequence in CRC and easy access to colonic epithelia or colonic epithelial cells through colonoscopy/colonic effluent provides the opportunity to study colonic stem cells early in course of natural history of the disease. With the advent of metagenomic sequencing, uncultivable organisms can now be identified in stool and their numbers correlated with the effects on colonic epithelia. It would be expected that these techniques would revolutionize our understanding of the racial disparity in CRC and pave a way for the same in other cancers as well. Unfortunately, this has not happened. Our understanding of the underlying factors responsible in African-Americans for higher incidence and mortality from colorectal carcinoma remains minimal. In this review, we aim to summarize the available data on role of microbiome and cancer stem cells in racial disparity in CRC. This will provide a platform for further research on this topic.

• Colorectal cancer
• Cancer stem cells
• Racial disparity
• Microbiome
• MiRNA

• I01 BX001927 BLRD VA
• R21 CA175916 NCI NIH HHS

• Colorectal cancer
• Copy number
• DNA methylation
• Epigenomics
• Exome sequencing
• Genomics
• Single nucleotide mutations

• ANXA11
• Bevacizumab
• Metastatic colorectal cancer
• PPP1R15A
• Predictive marker

• Animals
• Annexins/genetics
• Bevacizumab/therapeutic use
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Feasibility Studies
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis
• Polymorphism, Single Nucleotide
• Protein Phosphatase 1/genetics

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

• Colonoscopy
• Colorectal cancer
• Disparities
• Ethnic minorities
• Genetics
• Molecular biology
• Race-ethnicity
• Screening
• Underserved