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慢性炎症与结直肠癌及其他肥胖相关癌症的风险:健康、衰老与身体成分研究

Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.

作者信息

Izano Monika, Wei Esther K, Tai Caroline, Swede Helen, Gregorich Steven, Harris Tamara B, Klepin Heidi, Satterfield Suzanne, Murphy Rachel, Newman Anne B, Rubin Susan M, Braithwaite Dejana

机构信息

Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.

School of Public Health, University of California, Berkeley, CA.

出版信息

Int J Cancer. 2016 Mar 1;138(5):1118-28. doi: 10.1002/ijc.29868. Epub 2015 Oct 19.

Abstract

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.

摘要

慢性炎症与结直肠癌(CRC)及其他肥胖相关癌症(OBRC)风险之间关联的证据仍不一致,这可能是由于缺乏对炎症重复测量的研究。在基线时纳入2490名70 - 79岁成年人的健康ABC前瞻性研究中,我们评估了三种全身炎症标志物IL - 6、CRP和TNF - α的循环水平是否与CRC和OBRC的风险相关,OBRC包括胰腺癌、前列腺癌、乳腺癌和子宫内膜癌。在储存的空腹血样中测量炎症标志物。虽然仅可获得TNF - α的基线测量值,但在第2、4、6和8年还额外测量了IL - 6和CRP。采用多变量Cox模型来确定CRP和IL - 6的三分位数以及对数转换后的基线、更新和平均测量值,以及TNF - α的基线测量值是否与新发癌症风险相关。在中位随访11.9年期间,我们分别观察到55例CRC和172例OBRC病例。更新后的CRP最高三分位数组患CRC的风险比最低三分位数组高出两倍多(HR = 2.29;95% CI:1.08 - 4.86)。未发现结直肠癌与IL - 6或TNF - α之间存在显著关联。此外,总体上未发现肥胖相关癌症与这三种炎症标志物之间存在显著关联,但我们观察到BMI和非甾体抗炎药使用存在效应修饰的迹象。总之,在该人群中,较高的CRP水平与CRC风险增加相关,但与OBRC风险无关。这些发现提供了新的证据,即通过对该标志物的重复测量所反映的CRP长期升高水平可能在老年人结直肠癌发生过程中起作用。

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