Abstract: The disclosure features methods and compositions for determining whether a male subject has, or is at an increased risk of developing, an aggressive form of prostate cancer. The disclosure also features methods for adjusting a treatment regimen (e.g., discontinuing a therapy comprising an antioxidant) or administering a therapy that does not contain an antioxidant for a male subject in view of one or both of an MnSOD2 genotype status and an elevated level of an antioxidant in a biological sample obtained from the male subject. Also featured are methods for reducing superoxide levels in a subject based on one or both of an MnSOD2 genotype status and an elevated level of an antioxidant in a biological sample obtained from the male subject.