Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Nested case-control study of cancer, chromosomal aberrations, and genetic polymorphisms

DNA could not successfully be extracted from old microscopic slides, but cell suspensions, available from Italy, Denmark, and Norway, could be genotyped for GSTM1 and GSTT1 polymorphisms. The effect of these two genotypes on cancer risk prediction by chromosomal aberrations (CAs) was then assessed. An association between CA level and cancer risk was obvious in all subcohorts, but statistically significant only in Italy. The Italian cohort showed a much stronger association between CAs and cancer risk than the two other cohorts, probably reflecting the fact that the Italian results were based on re-scored CA data, and therefore the intra-laboratory technical variability was removed. No significant effect could be demonstrated for GSTM1 or GSTT1 genotype, although the small risk associated with low-penetrant risk genotypes and the small numbers of the study probably explain the lack of significant results. Neither of the polymorphisms affected cancer risk prediction by CAs. The small numbers prevented further analyses involving specific tumour sites and genotype interaction with smoking and other exposures. The negative findings - despite the size of the study - seem to support the conclusion that the effect of CAs in predicting cancer is independent on single genotypes. However, general conclusions may not be drawn from the present result representing only two major polymorphisms of similar nature. GST polymorphisms, similar to other polymorphisms of xenobiotic metabolism, may be important especially in connection with specific exposures. If many polymorphisms affect CA level, the effect of a single polymorphism on the cancer predictivity of CAs can be expected to be low. The results were reported in the Final Report and are being prepared for publication.

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Largo Rosanna Benzi, 10
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