Recent insights into the pathogenesis of colorectal cancer.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Internal Medicine, Division of Gastroenterology, Baylor Sammons Cancer Center, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas 75246, USA.
Ajay
A
Goel
Clement Richard
CR
Boland
D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D045647:DNA Glycosylases / Q000235:genetics; D053843:DNA Mismatch Repair; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D018570:Risk Assessment; D016019:Survival Analysis; D051820:TCF Transcription Factors / Q000235:genetics
D012333:RNA, Messenger; D051820:TCF Transcription Factors; D045647:DNA Glycosylases; D051718:MutS Homolog 2 Protein