Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause.
We conducted a nested case–control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35–54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case’s diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression.
After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5–24.9 kg/m2 (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m2 (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25–29.9 kg/m2 (OR: 0.98, CI: 0.39, 2.5, 138 cases).
Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.
From the aDepartment of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC; bEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC; and cVanderbilt University, Nashville, TN.
Submitted 10 June 2016; accepted 16 May 2017.
Supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES044005), the Avon Foundation (02-2012-085), and by the National Center for Advancing Translational Sciences (KL2-TR001109).
Preliminary data from this analysis were presented at the annual meeting of the American Society of Preventive Oncology, March 2016 in Columbus, OH.
Date availability: Investigators may apply to access the study data through the National Institute of Environmental Health Sciences Sister Study Tracking and Review System (STaRS) website at: https://www.sisterstudystars.org
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Correspondence: Hazel B. Nichols, Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, 135 Dauer Drive, Chapel Hill, NC 27599. E-mail: firstname.lastname@example.org.