Abstract
BackgroundBreast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls.Methodology/Principal FindingsTo obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56–0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34–0.36). High intake of antioxidants (OR 0.67–0.86, p = 0.04–0.05) and carotenoids (OR 0.68–0.86, p = 0.03–0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42–0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19–1.67, p = 0.07–0.17) to breast cancer.Conclusions/SignificanceBased on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet.
Highlights
Myeloperoxidase (MPO) is a microbicidal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during the phagocytosis
We investigated the breast cancer risk associated with MPOG463A polymorphism status in ethnically homogenous Caucasian women
Menopausal Status Our analysis has demonstrated that post-menopausal women carrying the low activity AA genotype were associated with nonsignificantly increased breast cancer risk whereas the risk associated with pre-menopausal women who carried the low activity AA genotype was significantly protective
Summary
Myeloperoxidase (MPO) is a microbicidal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during the phagocytosis. Levels of MPO-containing neutrophils are elevated in breast secretions as well as breast tissue with and without cancer [1,2,3]. It has been suggested that during chronic inflammation MPO is involved in DNA adduct formation through activation of heterocyclic amines to form chemically-reactive reactive oxygen species (ROS) in mammary epithelial cells [4]. Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls
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