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

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.

• Authors: Steffen Loft, Anja Olsen, Peter Møller, Henrik E Poulsen, Anne Tjønneland
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 22 Issue 7 Pg. 1289-96 (Jul 2013) ISSN: 1538-7755 [Electronic] United States
• PMID: 23658396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Receptors, Estrogen
• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Biomarkers, Tumor (urine)
• Breast Neoplasms (epidemiology, genetics, metabolism, urine)
• Case-Control Studies
• Cohort Studies
• DNA Damage
• Denmark (epidemiology)
• Deoxyguanosine (analogs & derivatives, urine)
• Diet
• Female
• Follow-Up Studies
• Humans
• Middle Aged
• Oxidative Stress (genetics, physiology)
• Postmenopause (genetics, urine)
• Prospective Studies
• Receptors, Estrogen (biosynthesis)
• Risk Factors