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标题：Heritable Susceptibility Factors for the Development of Cancer
其他标题：Heritable Susceptibility Factors for the Development of Cancer
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作者：William W. AU
期刊名称：Journal of Radiation Research
印刷版ISSN：0449-3060
电子版ISSN：1349-9157
出版年度：2006
卷号：47
期号：SupplementB
页码：13-17
DOI：10.1269/jrr.47.B13
摘要：High frequencies of inherited DNA sequence variations (polymorphisms) are found in the human population. The involvement of polymorphic genes (especially for chemical metabolism and DNA repair) in the development of cancer is under intensive investigation. In our studies, we have irradiated blood lymphocytes from normal non-smokers with γ-rays or UV-light to investigate genotypes and DNA repair functions. We found that XRCC1 399Gln and XRCC3 241Met were deficient in the repair of γ-ray-but not UV-light-induced DNA damage that led to the expression of chromosome aberrations; therefore the variant genotypes are defective in base excision repair. The reverse was found with XPD 312Asn and XPD 751Gln; therefore they are defective in nucleotide excision repair. XRCC1 194Trp, OGG1 326Cys and APE1 148Glu had no DNA repair deficiency based on our experimental conditions. In another study, we investigated the role of some of these genes on the development of lung cancer. We found a significant increase of chromosome aberrations in patients and controls that had the XPD 751Gln and GSTM1 null genotypes, indicating a mechanistic causation of the disease. Therefore, inheritance of susceptibility genes can have significant impact on disease burden in the population. On the other hand, there are many questions that need to be addressed in order to evaluate the impact of susceptibility on cancer. These questions include the understanding of combinations of different polymorphic genes for susceptibility and of specific disease susceptibility for different ethnic populations.
关键词：Genetic susceptibility; Polymorphic genes; Chemical metabolism; DNA repair; Cancer