Nechuta Sarah, Cai Qiuyin, Zheng Ying, Milne Ginger L, Cai Hui, Dai Qi, Yang Gong, Zheng Wei, Lu Wei, Shu Xiao Ou
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA,
Cancer Causes Control. 2014 Jun;25(6):701-7. doi: 10.1007/s10552-014-0373-7. Epub 2014 Mar 29.
Systemic oxidative stress has been implicated in the pathogenesis and progression of many chronic diseases, including breast cancer. No studies have investigated F2-isoprostanes (F2-IsoPs), valid biomarkers of systemic oxidative stress, in association with breast cancer prognosis. We conducted a nested case-control study in a prospective breast cancer survivor cohort to investigate systemic oxidative stress and survival.
Urinary levels of F2-IsoPs and its major urinary metabolite (2,3-dinor-5,6-dihydro-15-F2t-IsoP, F2-IsoP-M) were measured post-cancer treatment using gas chromatography/negative ion chemical ionization mass spectrometry for 57 deceased breast cancer patients (cases) and 103 surviving patients (controls) matched 1:2 on age at diagnosis, stage, and diagnosis year. Odds ratios (ORs) and 95 % confidence intervals (CIs) were derived from conditional logistic regression models.
In unadjusted models, elevated F2-IsoP levels categorized based on the median value [≥1.73; <1.73 (reference)] were nonsignificantly inversely associated with mortality (OR 0.51, 95 % CI 0.24-1.10). After adjustment for potential confounders, elevated F2-IsoP levels were significantly associated with mortality (OR 0.36, 95 % CI 0.14-0.96). The inverse association was marginally significant when F2-IsoP was categorized based on tertiles (p trend = 0.08). In contrast, elevated F2-IsoP-M levels, categorized based on the median level [≥0.91; < 0.91(reference)], were associated with a statistically nonsignificant increased risk of mortality in both unadjusted and adjusted models (adjusted OR 1.39, 95 % CI 0.62-3.09).
Results suggest a role for oxidative stress biomarkers in breast cancer survival; however, as this is the first study to date, additional larger studies are needed.
全身性氧化应激与包括乳腺癌在内的许多慢性疾病的发病机制和进展有关。尚无研究调查全身性氧化应激的有效生物标志物F2-异前列腺素(F2-IsoPs)与乳腺癌预后的关系。我们在一个前瞻性乳腺癌幸存者队列中进行了一项巢式病例对照研究,以调查全身性氧化应激与生存率的关系。
采用气相色谱/负离子化学电离质谱法,对57例已故乳腺癌患者(病例组)和103例存活患者(对照组)在癌症治疗后测定尿中F2-异前列腺素及其主要尿代谢产物(2,3-二去甲-5,6-二氢-15-F2t-异前列腺素,F2-IsoP-M)的水平,对照组与病例组按诊断年龄、分期和诊断年份1:2匹配。比值比(OR)和95%置信区间(CI)来自条件逻辑回归模型。
在未调整模型中,根据中位数[≥1.73;<1.73(参考值)]分类的F2-异前列腺素水平升高与死亡率呈非显著负相关(OR 0.51,95%CI 0.24-1.10)。在对潜在混杂因素进行调整后,F2-异前列腺素水平升高与死亡率显著相关(OR 0.36,95%CI 0.14-0.96)。当根据三分位数对F2-异前列腺素进行分类时,这种负相关具有边缘显著性(p趋势=0.08)。相比之下,根据中位数水平[≥0.91;<0.91(参考值)]分类的F2-IsoP-M水平升高,在未调整和调整模型中均与死亡率增加的风险无统计学显著相关性(调整后OR 1.39,95%CI 0.62-3.09)。
结果表明氧化应激生物标志物在乳腺癌生存中起作用;然而,由于这是迄今为止的第一项研究,需要更多更大规模的研究。