Non-Steroidal Anti-Inflammatory Drugs, DNA Repair and Cancer

摘要: Colorectal cancer is the third most common in women and fourth men, with respect to incidence, 529,000 deaths occurred worldwide 2002 (Parkin et al., 2005). Approximately 2 ‐ 5% of cases colorectal are due a genetic predisposition which hereditary non‐polyposis (HNPCC). HNPCC an autosomal dominant disorder high penetrance exhibits allelic locus heterogeneity (Aarnio 1995; de la Chapelle, 2004; Dunlop 1997). In there heterozygous germline mutations DNA mismatch repair (MMR) genes MutS homologue (MSH2), MutL 1 (MLH1), 6 (MSH6), post‐meiotic segregation increased (PMS2) (PMS1) (Bocker 1999; Buermeyer Jiricny, 1998; Jiricny & Marra, 2003; Lucci-Cordisco Mitchell 2002; Narayan Roy, Nicolaides Plaschke Zabkiewicz Clarke, 2004). Germline hMLH1 hMSH2 abnormalities these found more than 90% mutation carriers (Abdel-Rahman 2006; Hampel 2005; Lagerstedt Robinson 2007). The phenomenon transmission epimutation has also been reported (Hitchins MMR system plays essential role identifying correcting any replication errors additional arise through physical or chemical damage. These may be base‐base mismatches, short insertions/deletions heteroduplexes, can occur during recombination (Jiricny, 2003). therefore maintains genomic integrity stability essence provides tumour suppressor function. Deficiencies lead accumulation repetitive nucleotide regions, termed microsatellite instability (MSI) (Parsons 1993; Parsons Thibodeau 1998). Microsatellites classically defined as simple tandem sequence repeats – base pairs genome (Hancock, 1999). Changes number repeat units defective potentially causing (Riccio Yamamoto MSI phenotype error positive (RER+) considered almost canonical feature deficiency (Kinzler Vogelstein, 1996; 1993). This observed approximately 15% all human cancer, gastric endometrial carcinomas (Lothe Seruca Shibata, Umar 1994). Somatic inactivation largely