Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmö Diet and Cancer Cohort

Objective
Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association.
Methods
In the Malmö Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55–73 years at baseline (1991–96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression.
Results
Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47–0.90), 0.63 (0.45–0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43–0.99), p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05–2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer.
Conclusion
Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.

研究目的
尽管癌症可促进炎症发生，但炎症在肿瘤发生中的作用仍未得到充分阐明。本研究旨在探讨低度炎症是否与绝经后乳腺癌风险相关，以及肥胖是否会对这一关联产生调节作用。

研究方法
本研究基于马尔默饮食与癌症队列（Malmö Diet and Cancer cohort），于1991至1996年的基线阶段，在8513名基线时无癌症、年龄介于55~73岁的女性中开展嵌套病例对照研究；随访至2010年12月31日期间，共有459名女性被诊断为浸润性乳腺癌。我们对446例病例及885例按年龄、采血日期匹配的对照者的血液样本进行实验室分析，检测系统性炎症标志物：氧化型低密度脂蛋白（ox-LDL）、白细胞介素（interleukin，IL）-1β、IL-6、IL-8、肿瘤坏死因子（tumor necrosis factor，TNF）-α、白细胞计数、淋巴细胞及中性粒细胞。采用多变量条件logistic回归计算乳腺癌风险的比值比（OR）及95%置信区间（CI）。

研究结果
在完全校正模型中，氧化型低密度脂蛋白的第2、3三分位与乳腺癌呈负相关，其比值比（95%置信区间）分别为0.65（0.47~0.90）、0.63（0.45~0.89），趋势检验p值为0.01；肿瘤坏死因子-α的第3三分位同样呈现负相关关联，比值比为0.65（0.43~0.99），趋势检验p值为0.04。与之相反，IL-1β最高类别的人群乳腺癌风险更高，比值比为1.71（1.05~2.79），趋势检验p值为0.01。肥胖并未对炎症生物标志物与乳腺癌之间的关联产生调节作用。

研究结论
本研究未提示低度炎症会增加绝经后乳腺癌的发病风险。