Association between 8-oxo-7,8-dihydro-2'-deoxyguanosine Excretion and Risk of Postmenopausal Breast Cancer: Nested Case-Control Study.
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AbstractOxidative 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. Cancer Epidemiol Biomarkers Prev; 22(7); 1289-96. ©2013 AACR.
CitationCancer Epidemiol. Biomarkers Prev. 2013, 22 (7):1289-1296
SponsorsThe authors were supported for this work by the Danish Research Councils (S. Loft, A. Olsen, and P. Møller), Danish Cancer Society (A. Olsen), The Danish Ministry of the Interior and Health Research Centre for Environmental Health (S. Loft and A. Olsen) and ECNIS toward the establishment of a virtual European Centre for Research and Education on Cancer, Environment and Food (ECRECEF), European Commission FP7-KBBE-2010-4 grant no. 266198 (S. Loft and P. Møller).