Recently a T to C substitution in the mitochondrial targeting sequence of the manganese superoxide dismutase (MnSOD) gene was observed that changes the amino acid sequence of the protein from valine (V) to alanine (A) and is associated with a decreased defense capacity against oxidative stress. We investigated whether this polymorphism of the MnSOD gene is associated with increased risk for colorectal cancer among Hispanics and non-Hispanic whites. All controls (63 Hispanic, 58 non-Hispanic) and colorectal cancer cases (64 Hispanic, 61 non-Hispanic) were genotyped using a fluorogenic 5'-nuclease assay. The observed alanine frequency was 0.62 among disease-free Hispanics and 0.51 among non-Hispanic whites controls. No significant differences were observed between cancer patients and disease-free controls in either ethnic group (p=0.90) excluding this polymorphism as a risk factor for colorectal cancer in Hispanics and non-Hispanic whites. Among Hispanic individuals with colorectal cancer the alanine allele was observed more frequently in young patients. Patients homozygous for the alanine allele (24/64) showed a mean age of 37.6 years compared to 42.3 years for heterozygotes (29/64) and 48.4 years for patients homozygous for the V allele (p=0.045, ANOVA). The data demonstrate that the -9Val/-9Ala substitution is more common in Hispanics than in non-Hispanic whites. Furthermore, the data suggest that the alanine allele of this polymorphism may be associated with an increased risk to develop colorectal cancer at a young age in Hispanics.