Department of Public Health, Section of Enviromental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1289-96. doi: 10.1158/1055-9965.EPI-13-0229. Epub 2013 May 8.
Oxidative stress may be important in carcinogenesis and a possible risk factor for breast cancer. The urinary excretion of oxidatively generated biomolecules, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), represents biomarkers of oxidative stress, reflecting the rate of global damage to DNA in steady state.
In a nested case-control design, we examined associations between urinary excretion of 8-oxodG and risk of breast cancer in a population-based cohort of 24,697 postmenopausal women aged 50 to 64 years with 3 to 7 years follow-up. The accruing cases of breast cancer were matched to controls by age at diagnosis, baseline age, and hormone replacement therapy (HRT). Spot urine samples collected at entry was analyzed for 8-oxodG by high-performance liquid chromatography with electrochemical detection. Incidence rate ratio (IRR; 95% confidence intervals) based on 336 matched pairs with all information was estimated per unit increase in 8-oxodG divided by creatinine for all and estrogen receptor (ER) positive and negative breast cancers.
There was a borderline significant positive association between 8-oxodG and risk of all breast cancer (IRR: 1.08; 1.00-1.17 per unit increase in nmol/mmol creatinine). This association was significant with respect to the risk of ER-positive cancer (IRR: 1.11; 1.01-1.23) and among women not using HRT (IRR: 1.11; 0.97-1.26) or with low dietary iron intake (IRR: 1.10; 1.06-1.37 per unit increase) for all breast cancer.
We observed positive association between 8-oxodG excretion and risk of especially ER-positive breast cancer.
Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer.
氧化应激可能在致癌作用中很重要，并且是乳腺癌的一个潜在危险因素。氧化生成的生物分子（如 8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG））的尿排泄代表氧化应激的生物标志物，反映了 DNA 在稳定状态下的整体损伤速率。
在一项巢式病例对照设计中，我们在一个基于人群的 24697 名 50 至 64 岁绝经后妇女队列中检查了尿 8-oxodG 排泄与乳腺癌风险之间的关联，这些妇女随访了 3 至 7 年。随着乳腺癌病例的不断增加，通过年龄、基线年龄和激素替代疗法（HRT）来与对照组匹配。在进入时收集的尿液样本通过高效液相色谱法与电化学检测分析 8-oxodG。基于所有信息的 336 对匹配对，按每单位 8-oxodG 与肌酐的比值计算，估计所有乳腺癌、雌激素受体（ER）阳性和阴性乳腺癌的发病率比（IRR；95%置信区间）。
8-oxodG 与所有乳腺癌的风险呈正相关（IRR：1.08；1.00-1.17 单位增加）。这种关联在 ER 阳性癌症的风险方面具有显著意义（IRR：1.11；1.01-1.23），在未使用 HRT 的妇女中（IRR：1.11；0.97-1.26）或在低膳食铁摄入（IRR：1.10；1.06-1.37 单位增加）时，所有乳腺癌的风险都有显著意义。
我们观察到 8-oxodG 排泄与 ER 阳性乳腺癌风险之间存在正相关。
我们的结果表明，氧化应激导致 DNA 损伤对乳腺癌的发生很重要。
