Plasma florescent oxidation products and breast cancer risk: repeated measures in the Nurses' Health Study

Reactive oxygen species (ROS), normally generated through biologic processes, may damage DNA, lipids, and proteins. ROS are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress. Limited data suggest an association between oxidative stress and breast cancer. We evaluated pre-diagnostic plasma fluorescent oxidation products (FlOP), a global biomarker of oxidative stress, and breast cancer risk in a nested case-control study in the Nurses' Health Study. Participants provided two blood samples (1989-1990 and 2000-2002) (N = 18,743). 377 women developed breast cancer between the second collection and June 1, 2006. Cases were matched to 377 controls. Relative fluorescent intensity at three different excitation/emission wavelengths (FlOP_360, FlOP_320, FlOP_400) were quantified in both samples, providing distant (≥10 years before diagnosis) and proximate (≤6 years before diagnosis) measures of oxidative stress. We observed no association between FlOP and breast cancer risk in proximate or distant samples (e.g., proximate extreme quartiles: FlOP_360, RR 0.8, 95 % CI 0.5-1.3, p trend = 0.49; FlOP_320, RR 1.1, 95 % CI 0.7-1.7, p trend = 0.53; FlOP_400, RR 1.3, 95 % CI 0.8-2.0, p trend = 0.80). In general no association was observed when cross-classifying or averaging proximate and distant exposure (e.g., extreme quartile of averages: FlOP_360, OR 0.9, 95 % CI 0.6-1.4, p trend = 0.82; FlOP_400, OR 0.9, 95 % CI 0.6-1.4, p trend = 0.55), with the exception of a significant trend for average FlOP_320 (extreme quartiles, OR 1.6, 95 % CI 1.0-2.4, p trend = 0.02). We did not observe important associations between FlOP and breast cancer risk in this large prospective study, though our data suggest women with consistently high FlOP_320 may be at increased risk.