Colon cancer syndrome

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, with about 5% of cases associated with inherited mutations linked to colon cancer syndromes. The molecular basis of sporadic and inherited CRC involves two distinct pathways, one of chromosomal instability and one associated with microsateUite mstabifity. The original model of chromosome instability proposed in 1990 to explain the pathogenesis of most sporadic tumors (-85%) has been further characterized to reveal a complex chain of events whereby normal colon fining (mucosa) is transformed... 

FIGURE 14.22 High and low magnification of an invasive cecal adenocarcinoma from a 46-year-old patient with hereditary nonpolyposis colon cancer syndrome (Lynch syndrome). Neoplastic cell nuclei are completely devoid of MLH2 immunoreactivity, whereas cell nuclei of the surrounding stromal cells stain strongly. Only the complete absence of nuclear staining should be interpreted as a marker of a mismatch repair enzyme defect. 

As discussed earlier in this chapter, Lynch syndrome or hereditary nonpolyposis colon cancer syndrome (HNPCC) is a cancer predisposition syndrome caused by mutation of a mismatch repair gene. Immunohistochemistry can be used to screen for mutations in... 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

Keywords Colon cancer functional dyspepsia functional gastrointestinal disorders gastroesophageal reflux disease Helicobacter pylori infection inflammatory bowel disease irritable bowel syndrome liver transplantation pharmacogenetics. 

FLUOROURACIL ANTIPROTOZOALS -LEVAMISOLE t risk of hepatotoxicity and neurotoxicity despite t cytotoxic effects Antiphosphatase activity of levamisole may t fluorouracil cytotoxicity This combination has been used successfully in the treatment of colon cancer. Monitor FBC and LFTs regularly. Advise patients to report symptoms such as diarrhoea, numbness and tingling, and peeling of the skin of the hands and feet (hand-foot syndrome)... 

PMSl). The DNA located between the nick and the mismatch is removed by 3 to 5 or 5 to 3 exonucleases depending on whether the nick is 3 or 5 to the mismatch. The gap is then filled by DNA Pol III in E. coli (Fig. 10) by DNA Pol 5 in humans and is ligated. Mismatch repair increases the spontaneous mutation rate in E. coli and yeast. Humans defective in mismatch repair exhibit a cancer-prone syndrome called hereditary nonpolyposis colon cancer (HNPCC), and sporadic mutations of mismatch repair genes are also associated with up to 50% of all human cancers (42 4). 

Elevation of y-GT is found in cholestasis, liver cirrhosis, viral hepatitis, fatty liver, porphyria, toxic liver damage, pancreatitis and pancreatic cancer, myocardial infarction, nephrotic syndrome, diabetes mellitus, right heart failure, obesity, nicotine abuse, and brain tumours. There is a good correlation of y-GT with CEA in colon cancer, involving a metastatic spread to the liver - an increase in y-GT in neoplastic disease is likewise supportive of the diagnosis of hepatic metastases. 

Colon cancer is one of the main causes of cancer mortality in Western societies [150]. About 15-20% of colorectal tumors are causally determined by inheritance of genetic alterations such as the hereditary nonpolyposis colorectal cancer (HNPCC) and the syndrome familial adenomatous polyposis (FAP) [151,152]. Microsatellite instability, a characteristic of HNPCC, is caused by mutations in the genes essential for mismatch repair. The loss of mismatch repair has several consequences most crucially, the loss of proofreading and correction of small deletions and insertions. FAP is a rare autosomal dominant syndrome caused by an inherited mutation in the APC gene. The disease is characterized by the development of multiple colorectal adenomas, numbering from a few polyps to several thousands. 

Familial colon cancer represents the least understood pattern of colorectal cancer. Up to 25% of patients who develop colorectal cancer will have a family history of colorectal cancer. In these famihes, the frequency of colorectal cancer is too high to be considered sporadic, but the pattern is not consistent with an inherited syndrome. First-degree relatives of patients diagnosed with colorectal cancer have an increased risk of the disease that is at least two to four times that of persons in the general population without a family history. ... 

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