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

Research output: Contribution to journalArticle


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.


  • Harinakshi Sanikini
  • David C. Muller
  • Marisa Sophiea
  • Sabina Rinaldi
  • Antonio Agudo
  • Eric J. Duell
  • Elisabete Weiderpass
  • Kim Overvad
  • Anne Tjønneland
  • Jytte Halkjær
  • Marie Christine Boutron-Ruault
  • Franck Carbonnel
  • Iris Cervenka
  • Heiner Boeing
  • Rudolf Kaaks
  • Tilman Kühn
  • Antonia Trichopoulou
  • Georgia Martimianaki
  • Anna Karakatsani
  • Valeria Pala
  • Domenico Palli
  • Amalia Mattiello
  • Rosario Tumino
  • Carlotta Sacerdote
  • Guri Skeie
  • Charlotta Rylander
  • María Dolores Chirlaque López
  • Maria Jose Sánchez
  • Eva Ardanaz
  • Bas Bueno-de-Mesquita
  • Roel C.H. Vermeulen
  • Dagfinn Aune
  • Tammy Y.N. Tong
  • Nathalie Kliemann
  • Neil Murphy
  • Marc Chadeau-Hyam
  • Marc J. Gunter
  • Amanda J. Cross
External organisations
  • Imperial College London
  • International Agency for Research on Cancer, World Health Organization
  • Catalan Institute of Oncology
  • UiT The Arctic University of Norway, Tromsø
  • Cancer Registry of Norway, Institute of Population-Based Cancer Research
  • Karolinska Institutet
  • University of Helsinki
  • Aarhus University
  • Danish Cancer Society Research Center
  • University of Paris-Sud
  • Institut Gustave Roussy
  • Bicêtre Hospital
  • German Institute of Human Nutrition
  • German Cancer Research Centre
  • Hellenic Health Foundation, Athens
  • National and Kapodistrian University of Athens
  • Istituto Nazionale dei Tumori
  • University of Naples Federico II
  • Civic and M.P Arezzo Hospital
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • Murcia Regional Health Council
  • CIBER Epidemiology and Public Health (CIBERESP)
  • University of Murcia
  • University of Granada
  • Health Research Institute of Navarra (IDISNA)
  • Skåne University Hospital
  • National Institute for Public Health and the Environment (RIVM)
  • University Medical Center Utrecht
  • University of Malaya
  • Bjørknes University College
  • Oslo university hospital
  • University of Oxford
  • Folkhälsan Research Center
  • University of Paris-Saclay
  • Attikon University Hospital
  • Institute for Cancer Research, Prevention and Clinical Network (ISPRO)
  • Hospital Clínico Universitario San Cecilio
  • Navarre Public Health Institute (ISPN)
  • Utrecht University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Public Health, Global Health, Social Medicine and Epidemiology


  • cancer, esophageal, gastric, hormones, obesity, reproductive
Original languageEnglish
Pages (from-to)929-942
JournalInternational Journal of Cancer
Issue number4
Early online date2019 May 3
Publication statusPublished - 2020
Publication categoryResearch