Strong association between cancer and genomic inst

Authors: Christian Streffer

Publish Date: 2009/12/24

Volume: 49, Issue: 2, Pages: 125-131

PDF Link

Abstract

After a first wave of radiationinduced chromosomal aberrations a second wave appears 20–30 cell generations after radiation exposure and persists thereafter This late effect is usually termed “genomic instability” A better term is “increased genomic instability” This effect has been observed in many cell systems in vitro and in vivo for quite a number of biological endpoints The radiationinduced increase in genomic instability is apparently a general phenomenon In the development of cancer several mutations are involved With increasing genomic instability the probability for further mutations is enhanced Several studies show that genomic instability is increased not only in the cancer cells but also in “normal” cells of cancer patients eg peripheral lymphocytes This has for example been shown in uranium miners with bronchial carcinomas but also in untreated head and neck cancer patients The association between cancer and genomic instability is also found in individuals with a genetic predisposition for increased radiosensitivity Several such syndromes have been found In all cases an increased genomic instability cancer proneness and increased radiosensitivity coincide In these syndromes deficiencies in certain DNArepair pathways occur as well as deregulations of the cell cycle Especially mutations are seen in genes encoding proteins which are involved in the G1/Sphase checkpoint Genomic instability apparently promotes cancer development In this context it is interesting that hypoxia increased genomic instability and cancer are also associated All these processes are energy dependent Some strong evidence exists that the structure and length of telomeres is connected to the development of genomic instability

Keywords: