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.
Epidemiology. 2017 Sep;28(5):667-674. doi: 10.1097/EDE.0000000000000685.
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/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (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.
氧化应激的有害影响已被广泛认识，但细胞凋亡和衰老的诱导也可能有益于癌症预防。最近的研究表明，氧化应激可能与绝经前的乳腺癌风险较低有关。
我们在 NIEHS 姐妹研究队列（共 50884 名女性）中进行了一项巢式病例对照研究（457 例病例，910 例对照）。符合条件的入选者为年龄在 35-54 岁的绝经前女性。按年龄和入组年份对对照进行 2:1 配对，并在相应病例诊断时为乳腺癌阴性。氧化应激通过尿液 F2-异前列腺素和代谢物（15-F2t-异前列腺素-M）浓度进行测量。多变量条件逻辑回归计算比值比（OR）和 95%置信区间（CI）。
在对体重指数（BMI）和其他潜在混杂因素进行多变量调整后，F2-异前列腺素的 >90 百分位数（≥2.94ng/mgCr）与 <25 百分位数（1.01ng/mgCr）相比，乳腺癌的 OR 为 1.1（95%CI：0.65，1.7），代谢物的 OR 为 0.70（95%CI：0.43，1.1）。在诊断时为绝经前（353 例，OR：0.59，95%CI：0.34，1.0）或<46 岁（82 例，OR：0.15，95%CI：0.06，0.42）的女性中，较高的代谢物浓度与较低的乳腺癌风险相关。在 BMI 为 18.5-24.9kg/m（OR：0.47，95%CI：0.18，1.2，208 例）和>30kg/m（OR：0.71，95%CI：0.30，1.7，107 例）的女性中，代谢物与乳腺癌的 OR 呈反比，但在 BMI 为 25-29.9kg/m（OR：0.98，95%CI：0.39，2.5，138 例）的女性中并非如此。
与其他研究一起，我们的结果支持氧化应激与绝经前乳腺癌风险之间可能存在反比关系。
