Global patterns and trends in colorectal cancer incidence in young adults.

Objective: Early-onset colorectal cancer (CRC) is increasing in the USA despite rapid declines in older ages. Similar patterns are reported in Australia and Canada, but a comprehensive global analysis of contemporary data is lacking.

Design: We extracted long-term data from Cancer Incidence in Five Continents and supplemental sources to report on worldwide CRC incidence rates and trends by age (20-49 years and ≥50 years) through diagnosis year 2012 or beyond (Australia, Finland, New Zealand, Norway, Sweden, USA).

Barriers to Lynch Syndrome Testing and Preoperative Result Availability in Early-onset Colorectal Cancer: A National Physician Survey Study.

Objective: Although widely recommended, Lynch syndrome (LS) testing with tumor microsatellite instability (MSI) and/or immunohistochemistry (IHC) is infrequently performed in early-onset colorectal cancer (CRC), and CRC generally. Reasons are poorly understood. Hence, we conducted a national survey focusing on gastroenterologists, as they are frequently first to diagnose CRC, assessing testing barriers and which specialist is felt responsible for ordering MSI/IHC.

Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review.

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care.

New York Citywide Colon Cancer Control Coalition: A public health effort to increase colon cancer screening and address health disparities.

Background: Although screening for colorectal cancer (CRC) is a widely accepted concept nationally and screening rates are increasing, there are differences in screening rates between states and within states.

Methods: In an effort to increase screening rates and ensure equal access with respect to race/ethnicity, the New York City Department of Health and Mental Hygiene formed a coalition of stakeholders in 2003, with its primary focus on colonoscopy, to develop and implement strategies across the city to achieve this goal.

Results: From a screening colonoscopy rate of only 42% in 2003, these concerted efforts contributed to achieving a screening rate of 62% by 2007 and a screening rate of almost 70% in 2014 with the elimination of racial and ethnic disparities.

The intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner.

The histone deacetylase inhibitor (HDACi) sodium butyrate promotes differentiation of colon cancer cells as evidenced by induced expression and enzyme activity of the differentiation marker intestinal alkaline phosphatase (ALPi). Screening of a panel of 33 colon cancer cell lines identified cell lines sensitive (42%) and resistant (58%) to butyrate induction of ALP activity. This differential sensitivity was similarly evident following treatment with the structurally distinct HDACi, MS-275.

Increased screening colonoscopy rates and reduced racial disparities in the New York Citywide campaign: an urban model.

Objectives: In 2003, in response to low colonoscopy screening rates and significant sociodemographic disparities in colonoscopy screening in New York City (NYC), the NYC Department of Health and Mental Hygiene, together with the Citywide Colon Cancer Control Coalition, launched a multifaceted campaign to increase screening. We evaluated colonoscopy trends among adult New Yorkers aged 50 years and older between 2003 and 2007, the first five years of this campaign.

Methods: Data were analyzed from the NYC Community Health Survey, an annual, population-based surveillance of New Yorkers.

Deciphering the colon cancer genes--report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010.

The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.

Developing a quality screening colonoscopy referral system in primary care practice: a report from the national colorectal cancer roundtable.

The use of colonoscopy in colorectal cancer (CRC) screening has increased substantially in recent years. Media messages and changes in insurance reimbursement, as well as new screening guidelines from the American Cancer Society and the US Preventive Services Task Force, have contributed to this increase. Primary care providers (PCPs) are frequently responsible for making the recommendation and referral for screening.

An A13 repeat within the 3'-untranslated region of epidermal growth factor receptor (EGFR) is frequently mutated in microsatellite instability colon cancers and is associated with increased EGFR expression.

Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, pathologic, genetic, and epigenetic features distinct from microsatellite-stable CRC. Examination of epidermal growth factor receptor (EGFR) mRNA and protein expression levels in a panel of colon cancer cell lines identified strong expression of EGFR in multiple cell lines with MSI. Although no relationship between EGFR overexpression and the length of a CA dinucleotide repeat in intron 1 was observed, a variant A13/A14 repeat sequence within the 3'-untranslated region (3'-UTR) of the EGFR gene was identified, which was mutated by either mononucleotide or dinucleotide adenosine deletions in 64% of MSI cell lines and 69% of MSI colon tumors.

Planning the human variome project: the Spain report.

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts.

A del T poly T (8) mutation in the 3' untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC).

Background: We have previously published results indicating that decreased expression of CDK2-AP1 in MSI human colorectal cancer is associated with deletion mutations in the poly (T) 8 repeat sequence within the 3'-UTR of the CDK2-AP1 gene. In this study, we test the hypothesis that the del T mutation results in decreased CDK2-AP1 expression by causing reduced mRNA stability.

Methods: We introduced wild-type and mutant 3'-UTR sequences fused to a green fluorescent protein (GFP) gene separately into human CRC cell lines and quantified the expression of the GFP gene.

Erlotinib, an effective epidermal growth factor receptor tyrosine kinase inhibitor, induces p27KIP1 up-regulation and nuclear translocation in association with cell growth inhibition and G1/S phase arrest in human non-small-cell lung cancer cell lines.

Erlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been shown to have potent antitumor effects against human non-small-cell lung cancer (NSCLC) cell growth; however, the mechanism of such an effect is not elucidated. Here, we demonstrate that erlotinib-induced cell growth inhibition in EGFR high-expressing human H322 NSCLC cells was accompanied by G1/S phase arrest, which was largely caused by a decrease in expression of G1/S-related cyclins, suppression of activities of cyclin-dependent kinase (CDK) 2 and CDK4, induction of CDK inhibitor p27(KIP1), and retinoblastoma hypophosphorylation. To further understand the role of p27(KIP1) in G1/S arrest and cell growth inhibition by erlotinib, we determined its effect on the expression of p27(KIP1) at transcriptional and posttranscriptional levels.

A novel mutation detection approach of hMLH1 and hMSH2 genes for screening of colorectal cancer.

Background: Recently, Denaturing High-Performance Liquid Chromatography (DHPLC) has been widely used for mutation detection hMLH1 and hMSH2 genes due to reduced cost of analysis, accuracy, and high sample throughput. Unfortunately, one major drawback in screening the hMLH1 and hMSH2 genes with any analysis technique involves sample preparation. Additionally, there are limitations to this technique which include: (1) amplicons for hMLH1 and hMSH2 exons cannot be generated under the same PCR thermal cycler condition due to differences in the annealing temperatures of the traditional primer sets which drastically increases sample preparation time; (2) due to minimal changes in the DHPLC chromatogram when compared to the corresponding wild-type amplicon, there is a possibility to not detect a homozygous mutation; and (3) lack of specialized mutation analysis software for automated screening of the hMLH1 and hMSH2 genes with the Transgenomic Wave system.

Modulation of CDK2-AP1 (p12(DOC-1)) expression in human colorectal cancer.

We have previously demonstrated an association between microsatellite instability and decreased CDK2-AP1 (p12(DOC-1)) expression in human colorectal cancer (CRC) cell lines. In those same studies, induction of CDK2-AP1 expression promoted both cell cycle arrest and apoptosis. The goals of our present study were to better understand the mechanisms leading to reduced CDK2-AP1 expression in microsatellite unstable (MSI) CRC and to study further the effect of CDK2-AP1 modulation on cell proliferation and apoptosis utilizing RNA interference (RNAi) techniques.

Deleted in oral cancer-1 expression upregulates proapoptosis elements in microsatellite-unstable human colorectal cancer.

Background: We previously reported differential expression of the growth suppressor, deleted in oral cancer-1 (DOC-1), in microsatellite-unstable (MSI+) versus microsatellite-stable colorectal cancer (CRC) cell lines. MSI+ CRC cell lines demonstrated decreased DOC-1 expression and decreased apoptosis. Transfection of wild-type DOC-1 into an MSI+ cell line (SW48) resulted in increased apoptosis.

Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer.

The precise genetic mechanism of malignant transformation in DNA mismatch repair deficient, microsatellite-unstable colorectal cancer (CRC) has yet to be elucidated. We employed cDNA microarray to identify patterns of gene expression among CRC cell lines and to compare directly lines with and without microsatellite instability. This study was undertaken to test the hypothesis that microsatellite-unstable CRC cell lines demonstrate specific patterns of gene expression that differ significantly from those observed among microsatellite-stable CRC.

Demonstration of human telomerase reverse transcriptase in human colorectal carcinomas by in situ hybridization.

Telomerase activity is present in most malignant tumors and provides a mechanism for unlimited replication of neoplastic cells. Expression of the gene encoding human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene, is associated with telomerase activity, and it is overexpressed in most colorectal carcinomas. In the present study we assayed telomerase activity by the telomeric repeat amplification protocol (TRAP) and used in situ hybridization (ISH) and the reverse transcription polymerase chain reaction (RT-PCR) to study hTERT expression in colorectal carcinomas and adjacent normal tissues.