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Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Sanikini H 1 , Muller DC 1 , Sophiea M 1 , Rinaldi S 2 , Agudo A 3 , Duell EJ 3 Show all authors , Weiderpass E 4 , Overvad K 5 , Tjønneland A 6 , Halkjaer J 6 , Boutron-Ruault MC 7 , Carbonnel F 7 , Cervenka I 7 , Boeing H 8 , Kaaks R 9 , Kühn T 9 , Trichopoulou A 10 , Martimianaki G 10 , Karakatsani A 10 , Pala V 11 , Palli D 12 , Mattiello A 13 , Tumino R 14 , Sacerdote C 15 , Skeie G 4 , Rylander C 4 , Chirlaque López MD 16 , Sánchez MJ 17 , Ardanaz E 18 , Regnér S 19 , Stocks T 20 , Bueno-de-Mesquita B 1 , Vermeulen RCH 21 , Aune D 1 , Tong TYN 22 , Kliemann N 2 , Murphy N 2 , Chadeau-Hyam M 1 , Gunter MJ 2 , Cross AJ 1

Affiliations 

  • 1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 2 Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
  • 3 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
  • 4 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 5 Department of Public Health, Aarhus University, Aarhus, Denmark
  • 6 Danish Cancer Society Research Center, Copenhagen, Denmark
  • 7 CESP, Faculté de Médecine, Université Paris-Sud, Villejuif, France
  • 8 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany
  • 9 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 10 Hellenic Health Foundation, Athens, Greece
  • 11 Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 12 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy
  • 13 Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
  • 14 Cancer Registry and Histopathology Department, "Civic - M. P. Arezzo" Hospital, ASP, Ragusa, Italy
  • 15 Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy
  • 16 Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
  • 17 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
  • 18 Navarra Public Health Institute, Pamplona, Spain
  • 19 Institution of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden
  • 20 Department of Clinical Sciences, Lund University, Lund, Sweden
  • 21 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  • 22 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Int J Cancer, 2020 Feb 15;146(4):929-942.
PMID: 31050823 DOI: 10.1002/ijc.32386

Abstract

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

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

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