Abstract
Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associated with cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search of published data was made and 22 studies were recruited, covering 20,025 case and control subjects, for meta- analyses of the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. The data on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significant association with the risk of development in co-dominant models and dominant models, but not in the recessive model. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphisms with aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on four studies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant association between MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lung cancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associated with 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 any significant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from the current study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostate and esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrant further investigation.
Highlights
Manganese superoxide dismutase (MnSOD), a nucleus-encoded antioxidant enzyme localized exclusively in the mitochondria, catalyzes the dismutation of two molecules of a superoxide anion into water and hydrogen peroxide, primarily to protect mitochondrial components from superoxide damage
We found statistically significant associations between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer risk in the co-dominant models (Val/Ala versus Val/Val, OR = 1.11; 95% CI =1.01-1.22; Ala/Ala versus Val/Val, OR = 1.25; 95% CI = 1.03-1.51) and the dominant model (Val/Ala+Ala/Ala versus Val/Val, OR = 1.15; 95% CI = 1.01-1.31; Figure 1), but no significant association in the recessive model
In the subgroup analysis by disease stages (Table 1), there was no significant association of MnSOD with prostate cancer aggressiveness in the heterozygote model (Val/Ala versus Val/Val, OR = 1.21; 95% CI = 0.98-1.48), homozygote model (Ala/Ala versus Val/Val, OR = 1.27; 95% CI = 0.99-1.63), recessive model (Ala/Ala versus Val/Ala+Val/Val, OR = 0.98; 95% CI = 0.81-1.20), or dominant model (Val/Ala+Ala/Ala versus Val/Val, OR = 1.18; 95% CI = 0.97-1.44; Figure 2B)
Summary
Manganese superoxide dismutase (MnSOD), a nucleus-encoded antioxidant enzyme localized exclusively in the mitochondria, catalyzes the dismutation of two molecules of a superoxide anion into water and hydrogen peroxide, primarily to protect mitochondrial components from superoxide damage (the latter is a normal byproduct of respiration). A previous study demonstrated that breast cancer cells overexpressing the Ile allele had much higher MnSOD activity than that of the cells overexpressing the Thr allele (Zhang et al, 1999) This polymorphism is so rare in the population (< 0.05%) that it does not play any significant role in sporadic breast cancer development (Egan et al, 2003). Another common polymorphism of MnSOD is Val16Ala (rs4880), a substitution of T to C (thymine to cytosine) at nucleotide 47 resulting in change of the amino acid from valine (Val, GTT) to alanine (Ala, GCT) on the 16th residue of a 24-amino acid signal sequence (Cai et al, 2003; Wang et al, 2009).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
