Colorectal cancers carcinogenesis

Maihofner C, Charalambous MP, Bhambra U, Lightfoot T, Geisslinger G, Gooderham NJ (2003) Expression of cyclooxygenase-2 parallels expression of interleukin-Ibeta, interleukin-6 and NE-kappaB in human colorectal cancer. Carcinogenesis 24 665-671... 

S. cerevisiae aurora/IPllp, C. elegans aurora/AIR-2, and mammalian aurora B (also called AIM-1) phosphorylate H3 at Ser-10 and Ser-28 during mitosis [39 1] (Fig. 5). Protein phosphatase 1 removes the phosphate at these sites [39,42]. INCENP is bound to aurora B and is essential for the proper targeting of aurora B on the chromosomes [43-45]. INCENP and aurora B (AIM-1) are overexpressed in a variety of human cancers, including colorectal cancer [43,46]. Overexpression of aurora B (AIM-1) in CHE diploid fibroblasts leads to chromosomal instability, suggesting that aurora B overexpression may play a role in carcinogenesis [46]. INCENP/aurora B and H3 phosphorylation appear to be involved in assembly of mitotic chromosomes, but not mitotic chromosome compaction [44,47]. 

Fig. 2 Carcinogenesis. Environmental factors and molecular events involved in the initiation and progression of colorectal cancer...

A recent study by Mort et al. [71 ] showed that the NER genes XPD, XPF, XPG, and ERCCl, and the BER gene XRCCl are not important genetic determinants in colorectal carcinogenesis, while a modest association between colorectal cancer and a polymorphism in the recombination repair gene XRCC3 gene was found. 

Interestingly, Cryptosporidium infection has been related to carcinogenesis. The association of cryptosporidiosis and colonic adenocarcinoma was speculated in the case of a Spanish patient carrying both, who died rapidly after the onset of symptoms (Izquierdo et al. 1988). More recently, an epidemiological study in Poland reported a high frequency of cryptosporidiosis in patients with colorectal cancer (Sulzyc-Bielicka et al. 2007). However, in these reports it was unclear if Cryptosporidium sp. behaved as a carcinogenesis factor or simply as an opportunistic agent whose development was enhanced by host immunosuppression. 

Cancers with a high frequency of CpG transitions include colorectal cancer (45%), adenocarcinoma of the esophagus (48%) and stomach (34%), tumors of the brain (35%) and uterus (35%), and some hematopoietic malignancies (e.g., Burkitt s lymphoma (32%) (Fig. 3B). In colorectal carcinogenesis, p53 mutation is typically a relatively late event that correlates with the acquisition of an invasive potential (Fearon and Vogelstein, 1990). Acquisition of a CpG mutation in this context may be a consequence of deregulated cell proliferation, DNA instability, or altered nitric oxide metabolism. In the development of adenocarcinoma of the esophagus, however, mutations are often detectable in the preneoplastic lesion, Barrett s mucosa (Montesano et al., 1996). In the latter case, it has been speculated that... 

A Simple Model for Carcinogenesis of Colorectal Cancers with Microsatellite Instability... 

Deficiency in the DNA mismatch repair (MMR) pathway defines a variant subset of colorectal cancers (Lynch and Smyrk, 1996 Kinzler and Vogelstein, 1996). Replication errors (RER) are responsible for their main characteristic, the large-scale accumulation of frameshift mutations affecting microsatellite tracts (Lynch and Smyrk, 1996 Kinzler and Vogelstein, 1996), a phenomenon that is often referred to as microsatellite instability. The cancers without MMR deficiency will thereafter be called the common cancers, whereas the cancers with MMR deficiency will be alluded to as variant cancers. The RER phenotype can be acquired early in carcinogenesis, evidence... 

The proposed model of RER+ colorectal cancers suggests that the Lynch syndrome represents a new variation on the central theme of autosomal dominant cancer predisposition. Knudson s prediction of a shortened carcinogenesis among at-risk people applies to Lynch syndrome Sporadic RER+ CRCs exist and a subset of them have acquired mutations inactivating both alleles of a known MMR gene (B. Liu et al., 1995). On the other... 

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