Lung Cancer Susceptibility Genes

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1. The OGG1 gene

DNA repair genes are strong candidates as being responsible for susceptibility to human cancers, including lung cancer, since their polymorphisms can cause inter-individual differences in the capacity to prevent mutagenesis. We previously isolated the OGG1 gene encoding a glycosylase for 8-hydroxyguanine (8OHG), an oxidatively damaged promutagenic base, and identified a common single-nucleotide polymorphism (SNP), Ser326Cys, in it. OGG1-Cys326 was shown to have a lower ability to prevent mutagenesis by 8OHG than OGG1-Ser326. Case-control studies indicated that homozygotes for the OGG1-Cys326 allele have a higher risk for lung cancer than others. Association of this SNP with risks for lung and other cancers has been reproducibly observed by other groups.



2. Other DNA repair genes

By conducting case-control studies on 50 non-synonymous (associated with amino acid change) SNPs in 36 genes involved in diverse intracellular processes that maintain genome integrity, one SNP, POLI-Thr706Ala, three SNPs, LIG4-Ile658Val, TP53-Arg72Pro and REV1-Phe257Ser, and one SNP, MTH1-Val83Met, were identified as being associated with lung adenocarcinoma, squamous cell carcinoma and small cell carcinoma risks, respectively. The results indicated that inter-individual differences in the activity of multiple DNA repair pathways, including base excision repair, translational repair, and DNA strand break repair pathways, are involved in lung cancer susceptibility.