Manganese superoxide dismutase Ala-9Val polymorphism, environmental modifiers, and risk of breast cancer in a German population.

OBJECTIVE

A functional polymorphism at codon 16 (Alanine-to-Valine) of manganese superoxide dismutase (MnSOD) has been hypothesized to increase the risk of breast cancer and to modify the effects of oxidative stress. However, study findings have been inconsistent and sample sizes often small.

METHODS

We used a large population-based age-matched case-control study in German Caucasian women up to age 50 to assess breast cancer risk associated with this polymorphism and to investigate interaction with other known risk factors related to oxidative stress, including alcohol intake, cigarette smoking, and diet. Data on a total of 614 cases and 1,080 controls were evaluated using multivariate conditional logistic models.

RESULTS

No main effect between genotype and breast cancer was observed. However, risk was significantly increased for Ala carriers who consumed > or =19 g of alcohol per day, compared to women homozygous for the Val allele who did not drink (OR 2.1, 95% CI 1.1-3.9; p = 0.13 for interaction). No significant effect modification was observed for smoking or diet.

CONCLUSIONS

The MnSOD Ala-9Val polymorphism may contribute to an increase in breast cancer risk in the context of high alcohol consumption, however the polymorphism is not an overall risk factor for breast cancer in this primarily premenopausal population.