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

TY - JOUR

T1 - Association between 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion and risk of postmenopausal breast cancer

T2 - nested case-control study

AU - Loft, Steffen

AU - Olsen, Anja

AU - Møller, Peter

AU - Poulsen, Henrik E

AU - Tjønneland, Anne

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Cohort Studies

KW - DNA Damage

KW - Denmark

KW - Deoxyguanosine

KW - Diet

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Middle Aged

KW - Oxidative Stress

KW - Postmenopause

KW - Prospective Studies

KW - Receptors, Estrogen

KW - Risk Factors

KW - Tumor Markers, Biological

U2 - 10.1158/1055-9965.epi-13-0229

DO - 10.1158/1055-9965.epi-13-0229

M3 - Journal article

C2 - 23658396

SN - 1055-9965

VL - 22

SP - 1289

EP - 1296

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 7

ER -