Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort.

Jennifer Ose, Helena Schock, Anne Tjønneland, Louise Hansen, Kim Overvad, Laure Dossus, Françoise Clavel-Chapelon, Laura Baglietto, Heiner Boeing, Antonia Trichopolou, Vassiliki Benetou, Pagona Lagiou, Giovanna Masala, Giovanna Tagliabue, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H B As Bueno-de-Mesquita, Petra H M Peeters, N Charlotte Onland-Moret, Elisabete Weiderpass, Inger T Gram, Soledad Sánchez, Mireia Obon-Santacana, Maria-José Sànchez-Pérez, Nerea Larrañaga, José María Huerta Castaño, Eva Ardanaz, Jenny Brändstedt, Eva Lundin, Annika Idahl, Ruth C Travis, Kay-Tee Khaw, Sabina Rinaldi, Isabelle Romieu, Melissa A Merritt, Marc J Gunter, Elio Riboli, Rudolf Kaaks, Renée T Fortner

Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2016;24(6):951-61

PMID: 25855626

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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.

IMPACT

Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

Address: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.; Danish Cancer Society Research Center, Copenhagen, Denmark.; Department of Public Health, Section for Epidemiology Danish Cancer, Aarhus University, Aarhus, Denmark.; 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.; Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Australia.; Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.; 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.; Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, 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. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.; Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.; Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.; Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospita, ASP Ragusa, Italy.; Center for Cancer Prevention (CPOPiemonte), Turin, Italy. Human Genetic Foundation, Torino, Italy.; Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.; 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.; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.; 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.; Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.; Public Health Directorate, Asturias, Spain.; Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.; 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.; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Public Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, Spain.; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Navarre Public Health Institute, Pamplona, Spain.; Department of Surgery, Skåne University Hospital, Malmö, Sweden. Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.; Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.; Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.; Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; Biomarkers Group, International Agency for Research on Cancer, Lyon, France.; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [email protected].

DOI: 10.1158/1055-9965.EPI-14-1279-T