General Aspects of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.

Genetic and histological subtypes of gastric cancer reviewed, particularly emphasising on microsatellite instability and E-cadherin gene mutation

“…The MSI-H phenotype is reported in 5-50% of all GCs with significant differences within various ethnic groups [26,27]. The overwhelming majority of these are sporadic neoplasms with hypermethylation of CpG-rich gene promoters, thereby leading to transcriptional inactivation of a large number of genes, including MMR genes [11,22]. MicroRNAs have been shown to act as oncogenes or tumour suppressing genes in cancer, with putative growth-inhibitory functions undergoing promoter CpG island hypermethylation in human cancer [22].…”

“…Impaired MMR function leads to high-level MSI, which may be observed in both sporadic and hereditary cancers [10,22]. The MSI-H phenotype is reported in 5-50% of all GCs with significant differences within various ethnic groups [26,27].…”

“…MSIs are insertion and deletion mutations at microsatellites, because these structures are particularly prone to DNA replication. Microsatellites are defined as stretches of DNA sequences where a single nucleotide (mononucleotides) or units of two or more nucleotides are repeated in the genome [22]. There are at least 500,000 microsatellites in the human genome, either at intergenic or noncoding regions (with unknown functional significance) as well as in gene-encoding regions (coding microsatellites, cMSs).…”

“…The overwhelming majority of these are sporadic neoplasms with hypermethylation of CpG-rich gene promoters, thereby leading to transcriptional inactivation of a large number of genes, including MMR genes [11,22]. MicroRNAs have been shown to act as oncogenes or tumour suppressing genes in cancer, with putative growth-inhibitory functions undergoing promoter CpG island hypermethylation in human cancer [22]. Recognising the link between miR-155 with oncogenic function has been demonstrated through their specific downregulation of MLH1, MLH2 and MSH6 (core components of DNA mismatch repair), which has been implicated in the pathogenesis of HNPCC [22].…”

“…Insertions and deletions in cMSs result in the production of a truncated and therefore inactive protein. Examples of genes containing coding repeats that are targets for mutations in cancers with MSI, include genes associated with DNA repair (MLH1, MSH2, MSH6, PMS2), apoptosis (BAX, BCL10, Caspase-5), signal transduction (TGF-βRII, ACT RII) , cell cycle (PTEN, RIZ), and transcription factors (TCF-4) [22][23][24].…”