Abstract

To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9–1.5; OR = 1.5, 95% CI = 1.2–2.0; OR = 1.6, 95% CI = 1.2–2.1, for the 2nd, 3rd and 4th quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4th quartile versus lowest quartile OR = 2.0, 95% CI = 1.4–3.0), higher alcohol consumption (≥15 grams/day for 4th quartile versus lowest quartile OR = 2.3, 95% CI = 1.1–4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6–4.4 for 4th quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F2t-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2–2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.

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