Association between 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion and risk of postmenopausal breast cancer: nested case-control study

Background: 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. Methods: 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 50-64 year with 3-7 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 analysed for 8-oxodG by HPLC 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. Results: 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. Conclusion: We observed positive association between 8-oxodG excretion and risk of especially ER positive breast cancer. Impact: Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer.