hOGG1 Ser326Cys polymorphism and lung cancer susceptibility

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference i n complementation of mutant Escherichia coli that is defective in the repai r of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greate r in hOGG1-Ser(326) protein than in hOGG1(326) protein. Because many enviro nmental carcinogens produce 8-hydroxyguanine residue and mismatching to thi s modified base potentially causes oncogenic mutations, the capacity to rep air these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. ( a) Those with the Cys/Cys genotype were at an increased risk of squamous ce ll carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and t hose with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios fo r other histological subtypes of lung cancer or those in total were not sig nificant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not rea ch statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micrones ians, Melanesians, Hungarians, and Australian Caucasians), with much less p revalence of Cys allele in the latter three populations. Although our sampl e size was limited, these results indicate that the Ser326Cys variant may b e related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the ri sk is less than that previously reported to be associated with the CYP1A1 g ene. Further studies are needed to assess the importance of the interpopula tion variation to cancer susceptibility.