title: Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort.
abstract: BACKGROUND
  Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.
  
  
  METHODS
  We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.
  
  
  RESULTS
  CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity ≤ 0.01].
  
  
  CONCLUSIONS
  Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity.
  
  
  CONCLUSIONS
  Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors: Jennifer
authors: J
authors: Ose
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors: Helena
authors: H
authors: Schock
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Tjønneland
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Louise
authors: L
authors: Hansen
authors: Department of Public Health, Section for Epidemiology Danish Cancer, Aarhus University, Aarhus, Denmark.
authors: Kim
authors: K
authors: Overvad
authors: INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. Univ Paris Sud, UMRS 1018, Villejuif, France. IGR, Villejuif, France.
authors: Laure
authors: L
authors: Dossus
authors: INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. Univ Paris Sud, UMRS 1018, Villejuif, France. IGR, Villejuif, France.
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Australia.
authors: Laura
authors: L
authors: Baglietto
authors: Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
authors: Antonia
authors: A
authors: Trichopolou
authors: Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Vassiliki
authors: V
authors: Benetou
authors: Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors: Pagona
authors: P
authors: Lagiou
authors: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors: Giovanna
authors: G
authors: Masala
authors: Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors: Giovanna
authors: G
authors: Tagliabue
authors: Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospita, ASP Ragusa, Italy.
authors: Rosario
authors: R
authors: Tumino
authors: Center for Cancer Prevention (CPOPiemonte), Turin, Italy. Human Genetic Foundation, Torino, Italy.
authors: Carlotta
authors: C
authors: Sacerdote
authors: Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
authors: Amalia
authors: A
authors: Mattiello
authors: Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: H B As
authors: HB
authors: Bueno-de-Mesquita
authors: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Petra H M
authors: PH
authors: Peeters
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: N Charlotte
authors: NC
authors: Onland-Moret
authors: Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
authors: Elisabete
authors: E
authors: Weiderpass
authors: Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
authors: Inger T
authors: IT
authors: Gram
authors: Public Health Directorate, Asturias, Spain.
authors: Soledad
authors: S
authors: Sánchez
authors: Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors: Mireia
authors: M
authors: Obon-Santacana
authors: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Andalusian School of Public Health, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
authors: Maria-José
authors: MJ
authors: Sànchez-Pérez
authors: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Public Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, Spain.
authors: Nerea
authors: N
authors: Larrañaga
authors: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
authors: José María Huerta
authors: JM
authors: Castaño
authors: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Navarre Public Health Institute, Pamplona, Spain.
authors: Eva
authors: E
authors: Ardanaz
authors: Department of Surgery, Skåne University Hospital, Malmö, Sweden. Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
authors: Jenny
authors: J
authors: Brändstedt
authors: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors: Eva
authors: E
authors: Lundin
authors: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
authors: Annika
authors: A
authors: Idahl
authors: Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
authors: Ruth C
authors: RC
authors: Travis
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Biomarkers Group, International Agency for Research on Cancer, Lyon, France.
authors: Sabina
authors: S
authors: Rinaldi
authors: Biomarkers Group, International Agency for Research on Cancer, Lyon, France.
authors: Isabelle
authors: I
authors: Romieu
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Melissa A
authors: MA
authors: Merritt
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Marc J
authors: MJ
authors: Gunter
authors: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
authors: Elio
authors: E
authors: Riboli
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors: Rudolf
authors: R
authors: Kaaks
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. r.fortner@dkfz-heidelberg.de.
authors: Renée T
authors: RT
authors: Fortner
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000209:etiology / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000209:etiology / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000209:etiology / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000097:blood / Q000209:etiology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000209:etiology / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018836:Inflammation Mediators