The potentially functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase (hOGG1) gene has been implicated in lung cancer risk, but published studies have mixed findings. To summarize published data, we did a comprehensive meta-analysis. Two investigators extracted data independently from 17 case control studies published in the PubMed using the search phrases "hOGG1/OGG1/OGG and polymorphism/genetic variation and lung cancer." The meta-analysis included 6,375 cancer cases and 6,406 control subjects. The results showed that individuals carrying the hOGG1 Cys/Cys genotype did not have significantly increased risk of lung cancer [odds ratios (OR), 1.15; 95% (confidence interval) CI, 0.94-1.41] compared with those with the Ser/Ser genotype; similarly, no significant association with lung cancer risk was found either in the recessive (OR, 1.09; 95% CI, 0.90-1.32 for Cys/Cys versus Ser/Cys+Ser/Ser) or dominant model of the Ser326 allele (OR, 1.06; 95% CI, 0.93-1.21 for Cys/Cys+Ser/Cys versus Ser/Ser). However, significantly increased risks were found among Asian subjects (OR, 1.18; 95% CI, 1.01-1.38 for Cys/Cys+Ser/Cys versus Ser/Ser) in a dominant model. In stratified analyses by control source, compared with the Ser/Ser genotype, lung cancer risk associated with the hOGG1 Cys/Cys genotype was significantly increased in population-based studies (OR, 1.32; 95% CI, 1.04-1.67) but not in hospital-based studies (OR, 1.18; 95% CI, 0.98-1.42); in stratified analyses by the smoking status, however, the increased risk was observed only among nonsmokers in a dominant model (OR, 1.32; 95% CI, 1.04-1.67). The meta-analysis suggested that a careful matching should be considered in future larger genetic association studies including multiple ethnic groups.