Rossner Pavel, Terry Mary Beth, Gammon Marilie D, Agrawal Meenakshi, Zhang Fang Fang, Ferris Jennifer S, Teitelbaum Susan L, Eng Sybil M, Gaudet Mia M, Neugut Alfred I, Santella Regina M
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
J Cell Mol Med. 2007 Sep-Oct;11(5):1138-48. doi: 10.1111/j.1582-4934.2007.00097.x.
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 2(nd), 3(rd) and 4(th) 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 4(th) quartile versus lowest quartile OR = 2.0, 95% CI = 1.4-3.0), higher alcohol consumption (> or = 15 grams/day for 4(th) 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 4(th) 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 15F(2t)-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.
为研究氧化应激在乳腺癌风险中的作用,我们分析了1050例病例和1107例对照者的血浆蛋白羰基水平。我们发现,血浆蛋白羰基水平四分位数增加与乳腺癌风险存在统计学显著趋势(相对于最低四分位数,第二、第三和第四四分位数的OR分别为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,趋势P值 = 0.0001)。年轻(<50岁)和老年女性的风险增加相似,在身体活动水平较高的女性中更为明显(第四四分位数每周0.7小时相对于最低四分位数的OR = 2.0,95%CI = 1.4 - 3.0),酒精摄入量较高(第四四分位数每天≥15克相对于最低四分位数的OR = 2.3,95%CI = 1.1 - 4.7),以及使用激素替代疗法(HRT,第四四分位数相对于最低四分位数的OR = 2.6,95%CI = 1.6 - 4.4)。相乘交互项仅在身体活动和HRT方面具有统计学显著性。当分析仅限于采血前未接受化疗或放疗的女性时,也观察到血浆蛋白羰基水平与乳腺癌风险之间存在正相关。在对照者中,氧化蛋白水平随吸烟以及水果和蔬菜摄入量增加而显著升高,随每天酒精摄入量>30克而降低。与氧化应激两个标志物水平均低于中位数的女性相比,血浆蛋白羰基和尿15F(2t)-异前列腺素水平较高的女性患乳腺癌的风险增加80%(OR = 1.8,95%CI = 1.2 - 2.6)。总之,我们的结果表明血浆蛋白羰基水平升高可能与乳腺癌风险相关。