Novel genetic and epigenetic alterations in ... - Ous-research.no

IntroductionA rapidly growing field is the epigenetic control of micro-RNA (miRNA). miRNAs areendogenous non-coding small RNAs which regulate gene expression in a sequence-specificmanner, and can function as either oncogenes or tumor suppressor genes[47]. Compellingevidence now show that miRNAs are subject to both hypo- and hypermethylation in atumor and tissue-specific manner[48]. New studies also suggest that hypermethylation canmimic small chromosomal deletions or loss of heterozygosity by means of long rangeepigenetic silencing (LRES)[49;50]. The concept of LRES is no longer “one methylated CpGisland – one silent gene”, but rather involves large regions which may include severalgenes[49]. In breast cancer, the HOXA cluster has been shown to be subject to LRES, inwhich approximately 100kb DNA undergoes epigenetic inactivation[51].Colorectal cancerIncidence, treatment and outcome – Nature versus NurtureEach year over 1 million people are diagnosed with colorectal cancer (CRC) worldwide[52],including 3500 new Norwegian cases. It is an age-related disease, in the sense that it primarilyaffects older individuals (Figure 6). CRC is the most common form of sex-independentcancer ‡ , and the incidence is increasing (Figure 6). The disease is more prevalent in theindustrialized countries (Figure 7) § . Understanding both the initial and progressive steps ofthe disease is important in order to learn how and who to treat as knowledge of earlyalterations will provide information on how to detect the disease at an early, curable stage,while the later changes may be exploited to give information on treatment response. Thesubstantial differences in CRC incidence between the industrialized and developing countriessuggest that the disease is strongly affected by life-style and environmental factors. Severalrisk factors have been suggested and include obesity, high-fat diet, tobacco, alcohol and lackof physical activity[53]. Other factors have a preventive effect on CRC, e.g. exercise, highintake of fiber and vegetables as well as sufficient amounts of different nutrients. However,the literature is inconsistent on the matter, and the different mechanisms of risk factorexposure are still unknown[54].‡ The Norwegian Cancer Registry – http://www.kreftregisteret.no§ International Agency for Research on Cancer web pages - Cancer Mondial – http://www-dep.iarc.fr21