Inflammation is proposed to increase risk of developing
endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating
inflammation markers and
endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64
inflammation-related
biomarkers in 284 incident
endometrial cancer cases and 284 matched controls. Using multivariable logistic regression
inflammation markers were evaluated individually and combined into a cross-validated
inflammation score. Of 64 markers, 22 were associated with
endometrial cancer risk at p < 0.05 and 17 of 22 markers remained associated after multiple testing corrections. After adjusting for BMI and
estradiol, SERPINE1 [quartile(Q)4 vs. Q1 odds ratio (OR) (95% confidence interval (CI)), p trend = 2.43 (0.94-6.29), 0.03] and VEGFA [2.56 (1.52-4.30), 0.0002] were positively associated with
endometrial cancer risk, while CCL3 [0.46 (0.27-0.77), 0.01],
IL13 [0.55 (0.33-0.93), 0.01],
IL21 [0.52 (0.31-0.87), 0.01], IL1B [0.51 (0.30-0.86), 0.01] and IL23 [0.60 (0.35-1.03), 0.02] were inversely associated with risk. We observed large differences in
ORs across BMI-
inflammation score categories.
Endometrial cancer risk was most pronounced among obese women with the highest
inflammation score tertile (T) [10.25 (3.56-29.55) vs. normal BMI/T1]. Several
inflammation markers were prospectively associated with
endometrial cancer, including
adipokines, pro- and anti-inflammatory
cytokines, angiogenic factors and
acute phase proteins. Inverse associations with anti-inflammatory markers (
IL13,
IL21), other
inflammation markers/mediators (CCL3, IL1B, IL23), and a robust positive association between VEGFA and
endometrial cancer risk were independent of BMI and
estradiol, suggesting that these factors may influence risk through other mechanisms.