TY - JOUR
T1 - Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial
AU - Trabert, Britton
AU - Eldridge, Ronald C.
AU - Pfeiffer, Ruth M.
AU - Shiels, Meredith S.
AU - Kemp, Troy J.
AU - Guillemette, Chantal
AU - Hartge, Patricia
AU - Sherman, Mark E.
AU - Brinton, Louise A.
AU - Black, Amanda
AU - Chaturvedi, Anil K.
AU - Hildesheim, Allan
AU - Berndt, Sonja I.
AU - Safaeian, Mahboobeh
AU - Pinto, Ligia
AU - Wentzensen, Nicolas
N1 - Publisher Copyright:
© 2016 UICC
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
KW - circulating inflammation markers
KW - endometrial cancer
KW - nested case-contro
KW - prediagnostic
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U2 - 10.1002/ijc.30478
DO - 10.1002/ijc.30478
M3 - Article
C2 - 27770434
AN - SCOPUS:84999036899
SN - 0020-7136
VL - 140
SP - 600
EP - 610
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 3
ER -