Plasma matrix metalloproteinases and postmenopausal breast cancer risk: a nested case–control study in the Multiethnic Cohort study
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The survival of malignant breast cells depends upon the remodeling of the extracellular matrix, including complex interactions with matrix metalloproteinases (MMPs). It has been hypothesized that circulating MMPs may serve as early indicators of breast cancer development in hospital-based case–control studies. A nested case–control study of the association of pre-diagnostic plasma levels of MMPs with the subsequent risk of postmenopausal breast cancer was conducted within the Multiethnic Cohort. During the follow-up period, 713 women with incident invasive breast cancer were identified and individually (1:1) matched to controls. Four types of MMPs (1, 2, 3, and 7) were analyzed by microsphere immunofluorescence assay. Mean plasma levels of MMPs did not differ significantly between cases and controls; nor were there differences in breast cancer risk by MMP level. No difference in the risk of breast cancer by plasma level of the MMPs was found within strata of age, or ethnicity, although MMP-1 levels were positively associated with breast cancer risk in obese women and women by hormone replacement medications (P values for interaction <0.05). Few significant differences in risk by levels of the MMPs were found by any of the clinical variables. Circulating MMPs were not associated with postmenopausal breast cancer risk.
KeywordsBreast cancer Matrix metalloproteinases Body mass index Hormone replacement therapy Neoplasm staging Nested case–control study
The authors thank Jennifer F. Lai for the performance of the biochemical assays in the Analytical Biochemistry Share Resource of the University of Hawaii Cancer Center. This research was supported by NCI grants R37- CA54281, P01-CA33619, and P30-CA71789 from the National Cancer Institute.
The study was approved by the institutional review boards of the University of Hawaii and the University of Southern California.
Conflict of Interest
The authors declare that they have no conflict of interests.
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