Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associatedwith cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search ofpublished data was made and 22 studies were recruited, covering 20,025 case and control subjects, for metaanalysesof the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. Thedata on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significantassociation with the risk of development in co-dominant models and dominant models, but not in the recessivemodel. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphismswith aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on fourstudies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant associationbetween MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lungcancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associatedwith the decreased risk of lung cancer in the homozygote and dominant models, but not the heterozygote model.A subgroup analysis of the combination of MnSOD polymorphisms with tobacco smokers did not show anysignificant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from thecurrent study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostateand esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrantfurther investigation.