Abstract
Human 8-oxoguanine DNA glycosylase 1 (hOGG1) has a major role in the repair of 8-hydroxyguanine, a major promutagenic DNA lesion. The genetic polymorphism rs1052133, which leads to substitution of the amino acid at codon 326 from Ser to Cys, shows functional differences, namely a decrease in enzyme activity in hOGG1-Cys326. Although several studies have investigated the association between rs1052133 and lung cancer susceptibility, the effect of this locus on lung cancer according to histology remains unclear. We therefore conducted a case–control study with 515 incident lung cancer cases and 1030 age- and sex-matched controls without cancer, and further conducted a meta-analysis. In overall analysis, the homozygous Cys/Cys genotype showed a significant association with lung cancer compared to Ser allele carrier status (odds ratio (OR)=1.31, 95% confidence interval (CI)=1.02–1.69). By histology-based analysis, the Cys/Cys genotype showed a significantly positive association with small-cell carcinoma (OR=2.40, 95% CI=1.32–4.49) and marginally significant association with adenocarcinoma (OR=1.32, 95% CI=0.98–1.77). A meta-analysis of previous and our present study revealed that this polymorphism is positively associated with adenocarcinoma, although suggestive associations were also found for squamous- and small-cell lung cancers. These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung.
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Acknowledgements
We thank doctors, nurses, technical staff and hospital administration staff at ACCH for the daily administration of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center study. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan, for Cancer Research from the Ministry of Health, Labour and Welfare of Japan, and for the Third Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan.
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Okasaka, T., Matsuo, K., Suzuki, T. et al. hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type. J Hum Genet 54, 739–745 (2009). https://doi.org/10.1038/jhg.2009.108
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DOI: https://doi.org/10.1038/jhg.2009.108
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