Aspirin and other anti-inflammatory drugs prevent colorectal cancer (CRC) in some people but not others, according to the March issue of Gastroenterology. Andrew Chan et al. found that these drugs reduce the risk of CRC only in women with high levels of soluble tumor necrosis factor receptor 2 (sTNFR-2), a protein that mediates inflammation.
Chronic inflammation of the intestine and colon is associated with CRC. Many studies have found that people who regularly use aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil) or naproxen (Aleve), have a lower risk of CRC and adenomatous polyps, although results vary among studies.
Chan et al. measured levels of different markers of inflammation in blood samples collected from 32,826 women who participated in the Nurses’ Health Study from 1989 to 1990. Then they monitored their health until 2004.
The authors found that women with high plasma levels of sTNFR-2 had the greatest incidence of CRC. However, among these women, those who began taking aspirin or NSAIDs after the blood samples were collected had significant reductions in CRC incidence (multivariate relative risk of 0.39). Cancer incidence was not affected by drug use among women with low levels of sTNFR-2. This supports the hypothesis that aspirin and NSAIDs, at least in part, reduce risk of colorectal neoplasia through anti-inflammatory pathways.
Chronic inflammation is characterized by abnormal production of circulating inflammatory factors that have been linked with obesity, diabetes and vascular disease. However, Chan et al. did not associate other markers of inflammation, such as C-reactive protein or interleukin-6, with CRC risk. Because the researchers collected blood samples at only 1 timepoint, they were not able to monitor the levels of these markers over time or associate them with drug use.
Another limitation of this study is that it included only women—several studies have reported differences in inflammatory markers between women and men. Further studies are therefore needed to identify other markers of inflammation that change with use of anti-inflammatory drugs and that are associated with CRC risk in men—as well as with other types of cancer.
Chan et al. propose that sTNFR-2, however, is a good marker of the specific proinflammatory environment that predisposes people to cancer—this was the first study to directly examine its relationship with CRC risk. Moreover, sTNFR-2 might be a marker of deregulated insulin resistance pathways, because TNF regulates insulin signaling. Insulin resistance has been proposed as another factor that promotes colorectal carcinogenesis.
Chan et al. propose that inflammatory markers might be used to identify individuals who are most likely to receive cancer-prevention effects from anti-inflammatory drugs. Certain subsets of the population, defined by inflammatory markers, might obtain different benefits from anti-inflammatory drugs.
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Read the article online. This article has accompanying CME.
Chan AT, Ogino S, Giovannucci EL, et al. Inflammatory markers are associated with risk of colorectal cancer and chemopreventative response to anti-inflammatory drugs. Gastroenterology 2011;140:799–808.e2.