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EPIC: C-reactive protein, interleukin 6, IL-1 receptor antagonist associated with endometrial cancer risk in obese patients
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European researchers said treating chronic inflammation may reduce the risk for endometrial cancer in obese patients, based on results from a nested case-controlled study in the EPIC trial.
“Elevated pre-diagnostic levels of the inflammatory markers C-reactive protein, interleukin-6 and IL-1 receptor antagonist were associated with an increased risk of endometrial cancer,” the researchers concluded. “Our results provide some degree of support to the hypothesis that chronic inflammation, through its association with insulin resistance and estrogen production, but also independently of these two pathways, might mediate the obesity-related increase in risk of endometrial cancer, although after adjustment for BMI, the associations were weaker and no longer statistically significant.”
EPIC is a multicenter, prospective study exploring the associations between cancer incidence and nutritional, lifestyle, metabolic and genetic risk factors. The study included 10 countries, approximately 370,000 women and 150,000 men. Roughly 246,000 women and 140,000 men also provided blood samples.
In this nested cohort study, Dossus and colleagues selected 305 women in EPIC who developed endometrial cancer and 574 matched controls. Women whose endometrial cancers were not primary cancers, those who had a diagnosis of non-epithelial tumors and those who had undergone a hysterectomy were also excluded.
On average, the women diagnosed with endometrial cancer had a higher BMI than controls, 27.5 vs. 26.
When researchers tested cytokine levels in blood samples, they found a correlation between BMI and C-reactive protein (r=0.37; 95% CI, 0.29–0.44), IL-6 (r=0.32; 95% CI, 0.24–0.39) and IL-1 receptor antagonist (r=0.18; 95% CI, 0.10–0.26). The markers were also correlated with waist circumference for C-reactive protein (r=0.43; 95% CI, 0.35–0.50), IL-6 (r=0.35; 95% CI, 0.27–0.43) and IL-1 receptor antagonist (r=0.24; 95% CI, 0.15–0.32).
Conditional logistic regression analyses showed an association among all three markers and increased risk for endometrial cancer. OR was 1.58 (95% CI, 1.03–2.41) for the highest quartile of C-reactive protein compared with the lowest quartile. OR was 1.66 (95% CI, 1.08–2.54) for the highest vs. the lowest quartile of interleukin, and 1.82 (95% CI, 1.22–2.73) for the highest vs. the lowest category of IL-1 receptor antagonist.
After adjusting for BMI, researchers found that these estimates were no longer statistically significant, as was also the case after adjusting for waist circumference.
The message is, it’s obesity per se, not inflammation, that is a significant risk factor for endometrial cancer. That’s not astonishing in that patients with chronic rheumatological, inflammatory disorders are not hyper-susceptible. One might predict an ‘epidemic’ of this (and breast) cancer is on the horizon.
– Harry S. Jacob, MD
HemOnc Today Chief Medical Editor
For more information:
- Dossus L. Endocr Related Cancer. 2010;doi:10.1677/ERC-10-0053.