title: Plasma matrix metalloproteinase 2 levels and breast cancer risk.
abstract: Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000-2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study.
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States. Electronic address: saroner@hsph.harvard.edu.
authors: Sarah A
authors: SA
authors: Aroner
authors: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Bernard A
authors: BA
authors: Rosner
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Rulla M
authors: RM
authors: Tamimi
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Shelley S
authors: SS
authors: Tworoger
authors: Natural and Medical Sciences Institute, University of Tuebingen, Reutlingen, Germany.
authors: Nadja
authors: N
authors: Baur
authors: Natural and Medical Sciences Institute, University of Tuebingen, Reutlingen, Germany.
authors: Thomas O
authors: TO
authors: Joos
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, United States.
authors: Susan E
authors: SE
authors: Hankinson
mesh_terms: D001943:Breast Neoplasms / Q000097:blood* / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Breast cancer; Matrix metalloproteinases; Nested case–control; Plasma; Risk