Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

Genetic polymorphisms and frequency of cytogenetic biomarkers

Chromosomal aberrations (CAs) and micronuclei (MN) may be indicative of cancer risk because they reflect individual susceptibility factors. Inherited susceptibility to chromosome damage was assessed by genotype analysis using DNA extracted from fresh or frozen methanol-acetic acid fixed cell samples archived in the participating laboratories. The cell material available for the studies was derived from Belgium, Czech Republic, Finland, Hungary, and Norway. For the subjects, data on CAs, MN, or sister chromatid exchanges (SCEs) were available. Several polymorphisms of XMEs, DNA repair proteins, and enzymes of folate metabolism were able to affect the level of CAs and MN. For both CAs and MN, several polymorphisms seemed to interact with smoking and in some cases interaction with age was seen. Few polymorphisms appeared to have an impact on the frequency of SCEs. The complex findings probably reflect the multiple external and internal exposures inducing a multitude of DNA lesions eventually resulting in CAs and MN. Polymorphisms affecting the level of cytogenetic biomarkers can be viewed as potential factors influencing the cancer risk predictivity of CAs and MN. The magnitude of this tentative effect on cancer risk could not, however, be estimated, because genotype data were not available for most polymorphisms of interest in most cancer cases and controls of whom cytogenetic analyses were available. In the future, creation of a database combining genotype data and cytogenetic data from various European laboratories will make it possible to identify genotype combinations (or haplotypes) associated with exceptionally high rates of chromosome damage. The data collected in the present study will form an excellent starting point for such a database which is expected to be one step further towards the identification of genotypes that could markedly contribute to the association between chromosome damage and cancer risk. A number of scientific publications on the association of chromosome damage and genetic polymorphisms were published by the consortium during the project.

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