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Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort

Gasull M 1 , Pumarega J 2 , Kiviranta H 3 , Rantakokko P 3 , Raaschou-Nielsen O 4 , Bergdahl IA 5 Show all authors , Sandanger TM 6 , Goñi F 7 , Cirera L 8 , Donat-Vargas C 9 , Alguacil J 10 , Iglesias M 11 , Tjønneland A 4 , Overvad K 12 , Mancini FR 13 , Boutron-Ruault MC 13 , Severi G 13 , Johnson T 14 , Kühn T 15 , Trichopoulou A 16 , Karakatsani A 17 , Peppa E 16 , Palli D 18 , Pala V 19 , Tumino R 20 , Naccarati A 21 , Panico S 22 , Verschuren M 23 , Vermeulen R 24 , Rylander C 6 , Nøst TH 6 , Rodríguez-Barranco M 25 , Molinuevo A 7 , Chirlaque MD 26 , Ardanaz E 27 , Sund M 28 , Key T 29 , Ye W 30 , Jenab M 31 , Michaud D 32 , Matullo G 33 , Canzian F 34 , Kaaks R 14 , Nieters A 35 , Nöthlings U 36 , Jeurnink S 37 , Chajes V 31 , Matejcic M 31 , Gunter M 31 , Aune D 32 , Riboli E 32 , Agudo A 38 , Gonzalez CA 38 , Weiderpass E 39 , Bueno-de-Mesquita B 40 , Duell EJ 38 , Vineis P 41 , Porta M 42

Affiliations 

  • 1 Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • 2 Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • 3 National Institute for Health and Welfare, Department of Health Security, Kuopio, Finland
  • 4 Danish Cancer Society Research Center, Copenhagen, Denmark
  • 5 Department of Biobank Research, Umeå University, Umeå, Sweden; Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  • 6 Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway
  • 7 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain
  • 8 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain
  • 9 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 10 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Universidad de Huelva, Huelva, Spain
  • 11 Department of Pathology, Hospital del Mar (PSMar), Barcelona, Spain
  • 12 Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
  • 13 CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France
  • 14 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 15 Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain
  • 16 Hellenic Health Foundation, Athens, Greece
  • 17 Hellenic Health Foundation, Athens, Greece; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
  • 18 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
  • 19 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 20 Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy
  • 21 Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy
  • 22 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  • 23 Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 24 Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
  • 25 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
  • 26 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Murcia, Spain
  • 27 CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
  • 28 Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
  • 29 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 30 Department of Biobank Research, Umeå University, Umeå, Sweden; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden
  • 31 Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
  • 32 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 33 Department Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM/HuGeF, Torino, Italy
  • 34 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 35 Center for Chronic Immunodeficiency, Molecular Epidemiology, University Medical Center Freiburg, Freiburg, Germany
  • 36 Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
  • 37 Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 38 Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain
  • 39 Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • 40 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 41 Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 42 Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: [email protected]
Environ Res, 2019 Feb;169:417-433.
PMID: 30529143 DOI: 10.1016/j.envres.2018.11.027

Abstract

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.

OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.

METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.

RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.

CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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