Inflammation and Cancer Mortality

A recent article in Lancet detailed a possible link between chronic inflammation and lung cancer mortality.¹ The research is a secondary arm of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). The primary arm of CANTOS tested the effects of the drug canakinumab on patients who had experienced cardiovascular events. The interleukins are part of the inflammatory cascade seen in chronic inflammatory diseases. Canakinumab is an interleukin-1-β cytokine-blocking agent. Of interest to the dental community is that studies from the 1990s indicate a positive relationship between inflammatory periodontal disease and one group of interleukins. The CANTOS data was compiled from a randomized, double-blind, placebo-controlled trial. The researchers found 10,061 patients who previously had a myocardial infarction (MI).

Subjects were assigned into four groups. One received a placebo, while the others received various dosages of canakinumab delivered subcutaneously every three months. The results were encouraging in that these individuals — all of whom had previously experienced MI — had fewer subsequent heart attacks than those in the placebo group.

IF OTHER STUDIES REPORT SIMILAR RESULTS, THIS COULD HAVE SIGNIFICANT EFFECTS ON HUMAN MORTALITY

Reporting on the secondary arm of CANTOS, Ridker et al¹ presented data on subjects who had experienced MI events, but were free of previously diagnosed lung cancer when the study began. All had elevated levels of high-sensitivity C-reactive protein (hsCRP), which is produced by the liver and serves as a marker for chronic inflammation. The team found significantly higher baseline concentrations of hsCRP and interleukin 6 in subjects who were later diagnosed with lung cancer than in those who did not develop it. In the canakinumab groups, concentrations of hsCRP were reduced between 26% and 41%. Total cancer mortality was significantly lower in those who received the highest dosage of the drug. If other studies report similar results, this could have significant effects on human mortality.

One downside is that canakinumab reduces the body’s ability to fight infection. Compared to the control group, fatal infections or sepsis were significantly increased in the groups receiving the drug. Additional challenges include the need to inject these medications every three months and the associated costs.

This paper joins other studies published in recent years exploring the relationship of chronic inflammation and systemic disease. Besides the personal relevance for health professionals, there are possible applications for patients with periodontal disease. This class of drugs has the potential for local application around teeth and implants with chronic inflammatory disease. Yet, until canakinumab or similar drugs are available, clinicians should bear in mind that increased levels of hsCRP have been related to chronic infections, including periodontitis. A growing number of papers have suggested that treating inflammatory periodontal lesions can, in fact, reduce the probability of systemic diseases seen secondary to chronic inflammation. The ability to use similar medications, delivered locally to treat periodontitis and peri-implantitis, could be profound.

Thomas G. Wilson Jr., DDS
Editor in Chief
twilson@belmontpublications.com

REFERENCE

1. Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1-β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomized, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–1842.

From Decisions in Dentistry. December 2017;3(12):8.