Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Gastroenterology. 2011 Mar;140(3):799-808, quiz e11. doi: 10.1053/j.gastro.2010.11.041. Epub 2010 Nov 27.
BACKGROUND & AIMS: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of colorectal cancer (CRC). We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflammatory markers.
We measured levels of high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, and the soluble tumor necrosis factor receptor 2 (sTNFR-2) in blood samples from 32,826 women, collected from 1989 to 1990. Through 2004, we documented 280 cases of incident CRC; each case was matched for age to 2 randomly selected participants without cancer (controls). Information on anti-inflammatory drug (aspirin and NSAIDs) use was collected biennially.
Compared with women in the lowest quartile of plasma levels of sTNFR-2, women in the highest quartile had an increased risk of CRC (multivariate relative risk [RR], 1.67; 95% confidence interval [CI], 1.05-2.68; P for trend = .03). Among women with high baseline levels of sTNFR-2, those who initiated aspirin/NSAID use after blood collection had significant reductions in subsequent risk of CRC (multivariate RR, 0.39; 95% CI, 0.18-0.86). In contrast, among women with low baseline levels of sTNFR-2, initiation of aspirin/NSAID use was not associated with significant risk reduction (multivariate RR, 0.86; 95% CI, 0.41-1.79). Plasma levels of CRP and IL-6 were not significantly associated with CRC risk.
Plasma levels of sTNFR-2, but not CRP or IL-6, are associated with an increased risk of CRC. Anti-inflammatory drugs appear to reduce risk of CRC among women with high, but not low, baseline levels of sTNFR-2. Certain subsets of the population, defined by inflammatory markers, may obtain different benefits from anti-inflammatory drugs.
阿司匹林和非甾体抗炎药（NSAIDs）可降低结直肠癌（CRC）的风险。我们研究了血浆炎症标志物是否与 CRC 风险相关，以及抗炎药物的使用是否根据炎症标志物的水平与 CRC 风险呈不同相关性。
我们测量了 32826 名女性血液样本中的高敏 C 反应蛋白（CRP）、白细胞介素（IL）-6 和可溶性肿瘤坏死因子受体 2（sTNFR-2）水平，这些样本采集于 1989 年至 1990 年。通过 2004 年，我们记录了 280 例 CRC 新发病例；每个病例都与年龄相匹配，随机选择了 2 名没有癌症的参与者（对照组）。我们每两年收集一次关于抗炎药物（阿司匹林和 NSAIDs）使用情况的信息。
与 sTNFR-2 血浆水平最低四分位数的女性相比，sTNFR-2 血浆水平最高四分位数的女性 CRC 风险增加（多变量相对风险 [RR]，1.67；95%置信区间 [CI]，1.05-2.68；P 趋势 =.03）。在基线 sTNFR-2 水平较高的女性中，在采血后开始使用阿司匹林/NSAID 的女性 CRC 风险显著降低（多变量 RR，0.39；95%CI，0.18-0.86）。相比之下，在基线 sTNFR-2 水平较低的女性中，开始使用阿司匹林/NSAID 与 CRC 风险的显著降低无关（多变量 RR，0.86；95%CI，0.41-1.79）。CRP 和 IL-6 血浆水平与 CRC 风险无显著相关性。
sTNFR-2 血浆水平与 CRC 风险增加相关，但 CRP 或 IL-6 血浆水平与 CRC 风险无关。抗炎药物似乎可以降低基线 sTNFR-2 水平较高但不低的女性 CRC 的风险。根据炎症标志物定义的某些人群亚组可能会从抗炎药物中获得不同的益处。
