A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

Chunyan He, Rulla M. Tamimi, Susan E. Hankinson, David J. Hunter, Jiali Han

    Research output: Contribution to journalArticle

    39 Scopus citations

    Abstract

    Oxidative stress may be involved in breast carcinogenesis. Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species (ROS). A single nucleotide polymorphism (SNP) G-463A in the promoter region has been associated with a decrease in risk of breast cancer. We assessed the association between this polymorphism and breast cancer risk in a nested case-control study within the Nurses' Health Study (1,269 incident breast cancer cases and 1,761 matched controls). We further investigated potential gene-gene and gene-environment interactions. There were no significant associations between MPO or COMT genotypes and risk of breast cancer. However, the combination of a priori hypothesized low-risk genotypes in MPO and COMT genes was associated with a marginally significant decrease in breast cancer risk (OR, 0.28; 95% CI, 0.08-1.00). Dietary intake and plasma antioxidant levels may modify the association between the MPO polymorphism and breast cancer risk. Although the test for departure from multiplicative interaction was not significant, inverse associations with MPO genotype were more pronounced among women who consumed higher amounts of total fruits and vegetables (OR, 0.58; 95% CI, 0.30-1.12); this association was not found among the low-consumption group (OR, 1.11; 95% CI, 0.63-1.96). The relative risk associated with the MPO homozygous variant genotype was 0.44 (95% CI, 0.18-1.09) for women who had the highest level of plasma carotenoids. Results: from this study suggest that exogenous and endogenous modulators of oxidative stress may modify the association between the MPO polymorphism and breast cancer risk. Further research is needed to confirm these possible associations.

    Original languageEnglish (US)
    Pages (from-to)585-594
    Number of pages10
    JournalBreast Cancer Research and Treatment
    Volume113
    Issue number3
    DOIs
    StatePublished - Feb 1 2009

    Keywords

    • Antioxidant
    • Breast cancer
    • COMT (catechol-O-methyltransferase)
    • MPO (myeloperoxidase)
    • Oxidative stress

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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