title: Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.
abstract: 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.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Britton
authors: B
authors: Trabert
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Ronald C
authors: RC
authors: Eldridge
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Meredith S
authors: MS
authors: Shiels
authors: HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD.
authors: Troy J
authors: TJ
authors: Kemp
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHUQ) Research Center, Laval University, Faculty of Pharmacy, Québec, Canada.
authors: Chantal
authors: C
authors: Guillemette
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Patricia
authors: P
authors: Hartge
authors: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
authors: Mark E
authors: ME
authors: Sherman
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Louise A
authors: LA
authors: Brinton
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Amanda
authors: A
authors: Black
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Anil K
authors: AK
authors: Chaturvedi
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Allan
authors: A
authors: Hildesheim
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Sonja I
authors: SI
authors: Berndt
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Mahboobeh
authors: M
authors: Safaeian
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.|HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD.
authors: Ligia
authors: L
authors: Pinto
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors: Nicolas
authors: N
authors: Wentzensen
mesh_terms: D054392:Adipokines / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D016207:Cytokines / Q000097:blood; D055088:Early Detection of Cancer / Q000379:methods; D016889:Endometrial Neoplasms / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; D016207:Cytokines
keywords: circulating inflammation markers; endometrial cancer; nested case-contro; prediagnostic