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

Steffen Loft, Anja Olsen, Peter Møller, Henrik E Poulsen, Anne Tjønneland

47 Citations (Scopus)

Abstract

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 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. 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. Conclusions: 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.

Original languageEnglish
JournalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume22
Issue number7
Pages (from-to)1289-96
Number of pages8
ISSN1055-9965
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Breast Neoplasms
  • Case-Control Studies
  • Cohort Studies
  • DNA Damage
  • Denmark
  • Deoxyguanosine
  • Diet
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Oxidative Stress
  • Postmenopause
  • Prospective Studies
  • Receptors, Estrogen
  • Risk Factors
  • Tumor Markers, Biological

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