Colorectal cancer in men was not significantly associated with baseline plasma levels of three inflammatory markers – C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 (TNFR-2), investigators reported online in Cancer Epidemiology.

The nested case-control study included 268 colorectal cancer (CRC) cases and 446 controls matched by age and smoking status from the Physician’s Health Study, a prospective, randomized, placebo-controlled aspirin trial. High TNFR-2 levels were significantly linked with CRC risk in the placebo arm (relative risk, 1.77; 95% confidence interval, 1.02-3.06; P = .02) of the study, and not in the aspirin arm (P = .72), Chul Kim, MD, of University of Minnesota, Minneapolis, and his associates noted. “This may suggest that aspirin exerts its carcinoprotective effect by blocking the TNF-alpha pathway,” they added, noting that in mice, blocking this pathway helps prevent CRC secondary to chronic colitis. However, a test for interactions yielded no evidence that aspirin significantly modifies the relationship between TNFR-2 and CRC, they said ( Cancer Epidemiol. 2016;44:65-70 ).

Chronic inflammation is thought to promote carcinogenesis, including CRC, which is associated with inflammatory bowel disease. Studies have shown that long-term nonsteroidal anti-inflammatory and aspirin therapy attenuates CRC risk, but have not clarified the relationship between baseline plasma inflammatory markers and CRC. Dr. Kim and associates controlled for known CRC risk factors, including body mass index, alcohol consumption, physical activity level, multivitamin use, and dairy intake. In contrast to their findings in men, the Nurses’ Health Study did find a significant link between TNFR-2 levels and CRC risk in women, they noted (RR, 1.67; 95% CI, 1.05-2.68; P = .03).

They acknowledged several limitations. A single inflammatory marker test “may not represent a person’s inflammatory status during the development of colorectal cancer,” and marker levels were assayed during the run-in period of the trial, when all participants received aspirin, they said. Furthermore, the trial only ran for 5 years, after which more than 70% of patients took aspirin, which “would have significantly attenuated the true association that we would observe in this study.”

The National Cancer Institute, National Heart, Lung, and Blood Institute, National Cancer Institute of Canada, and National Institutes of Health provided funding. The authors had no disclosures.