Abstract
ABSTRACTA tissue bank is established in our department on a total of 659 persons whereof 341 are included in theNordic data base on somatic chromosome damage in humans. Genotyping of susceptibility genes relevantto the exposures of the cohort is an ongoing undertaking in our laboratory. GST's and mEH have beengenotyped for 80 persons so far, CYP's for 20 persons. When the mean number of chromatide breaks and ofcells with aberrations were related to genotypes no statistical difference could be observed between thegenotypes for either parameter. No difference in cytogenetic damage between exposed and referents orbetween smokers and non-smokers were identified for the two separate occupational studies these 80persons represent. The results of the various cytogenetic endpoints were trichotomized and compared to thegenotype distribution. Although not statistically significant, the observed trend with higher percentage ofpersons with polymorphic GSTp1 in particular, but also for GSTq1 and mEH (exon 4) in the group withhigh frequency of chromosome aberrations will be interesting to follow. For further follow-up studies, anested case-control study within the cohort would give a more rapid and less expensive approach thananalysing each study separately as a traditional case-control study. As high frequency of chromosomaldamage is associated with cancer development, the hypothesis to be tested would be whether genetic polymorphismsfor the most appropriate susceptibility genes could be an explanatory factor for this association.
Highlights
Whether a chemical contributes to cancer or other diseases depends on the extent of an individual's exposure, and on the effectiveness of the body's defence response
Knowledge about the chemicals is necessary in order to determine which susceptibility genes it would be important to test for, but potential effect of the gene differences are dependent upon the level of exposure as well
Even if the susceptibility genes studied are relevant to the chemicals of exposure, which they are in the present study, another important factor is the frequency distribution of the gene in the general population
Summary
Whether a chemical contributes to cancer or other diseases depends on the extent of an individual's exposure, and on the effectiveness of the body's defence response. Another class of genes, which is the focus of this paper, is dependent upon exposure to exert an effect These genes are called modifying genes in genetic terminology, and susceptibility genes in molecular epidemiology. Unlike the disease determining genes, the prevalence of susceptibility genes is often high in a population and the role of environmental exposure is crucial. They may impart relatively small risk, but since the frequencies are so high, the attributable risks can be high[4]
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