Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis

Abstract A growing body of evidence suggests that reactive oxygen species (ROS) play an important role in human cancers. Manganese superoxide dismutase ( MnSOD ) is the major antioxidant in the mitochondria, catalysing the dismutation of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterised functional polymorphism, Val-9Ala of MnSOD , a number of molecular epidemiological studies have evaluated the association between Val-9Ala and cancer risk. However, the results remain conflicting rather than conclusive. This meta-analysis on 15,320 cancer cases and 19,534 controls from 34 published case–control studies shows no significant overall main effect of MnSOD Val-9Ala on cancer risk. However, we found that the MnSOD 9Ala allele was associated with an increased prostate cancer risk (Val/Ala versus Val/Val: odds ratio (OR) = 1.1; 95% confidence intervals (CI): 1.0–1.3; Ala/Ala versus Val/Val: OR = 1.3; 95% CI: 1.0–1.6; Val/Ala + Ala/Ala versus Val/Val: OR = 1.2; 95% CI, 1.0–1.3). In addition, we found that the MnSOD Ala-9Ala genotype contributed to an increased breast cancer risk in premenopausal women who had low consumption of antioxidants (Ala/Ala versus Val/Ala + Val/Val: OR = 2.6, 95% CI: 1.0–6.4 with low vitamin C consumption; OR = 2.1, 95%CI: 1.3–3.4 with low vitamin E consumption and OR = 2.9, 95%CI: 1.5–5.7 with low carotenoid consumption). These results suggest that the MnSOD Val-9Ala polymorphism may contribute to cancer development through a disturbed antioxidant balance.