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Recent insights into the pathogenesis of colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the Western world, but our understanding of this disease is incomplete. The recent advent of new technologies has provided novel insights into the pathogenesis of CRC.Genome-wide association studies have recently linked CRC to 10 common genetic variants or single-nucleotide polymorphisms that map to chromosomes 8q23, 8q24, 10p14, 11q23, 14q22, 15q13, 16q22, 18q21, 19q13 and 20p1. However, the causal significance of these variants is not understood, and some are located in poorly characterized genomic regions or gene deserts. Recent studies indicate that the single-nucleotide polymorphism rs6983267, which maps to 8q24, serves as an enhancer of MYC expression by binding T cell factor 4 (TCF4) and influencing Wnt signaling. In addition, several microRNAs interact with genes such as K-RAS, APC, p53, PTEN, TCF4, COX-2, DNMT3a and DNMT3b. Germline hypermethylation of the DNA mismatch repair genes MLH1 and MSH2 may serve as predisposing events in some CRC patients.Recent studies have elucidated novel mechanisms involved in CRC, including the involvement of single-nucleotide polymorphisms not located within traditional genes, the role of microRNAs and epimutations in DNA mismatch repair genes. Interestingly, most of this progress has been made by understanding DNA that does not encode genes.

SUBMITTER: Goel A

PROVIDER: S-EPMC2846600 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Recent insights into the pathogenesis of colorectal cancer.

Goel Ajay A Boland Clement Richard CR

Current opinion in gastroenterology 20100101 1

<h4>Purpose of review</h4>Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the Western world, but our understanding of this disease is incomplete. The recent advent of new technologies has provided novel insights into the pathogenesis of CRC.<h4>Recent findings</h4>Genome-wide association studies have recently linked CRC to 10 common genetic variants or single-nucleotide polymorphisms that map to chromosomes 8q23, 8q24, 10p14, 11q23, 14q22, 15q13, 16q22, 18q21, 19 ...[more]

PMID: 19786869

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Project description:Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

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Recent insights into the pathogenesis of colorectal cancer.

Publications

Recent insights into the pathogenesis of colorectal cancer.

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