hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

作者：Haruhiko Sugimura, Takashi Kohno, Kenji Wakai, Kiyoko Nagura, Keiichiro Genka, H Igarashi, Billah Morris, S Baba, Yoshiyuki Ohno, Chang‐Ming Gao, Zaiming Li, Jiayi Wang, Toshiro Takezaki, K Tajima, Tibor V. Varga, Takeru Sawaguchi, J. Koji Lum, Jeremy Martinson, Shoichiro Tsugane, Teruo Iwamasa, Kazuya Shinmura, Jun Yokota · 发表于：PubMed · 年份：1999 · 被引用次数：236 · 研究领域：DNA Repair Mechanisms、Carcinogens and Genotoxicity Assessment、Cancer-related Molecular Pathways

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 in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair 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 cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those 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 for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach...