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

Harinakshi Sanikini, David C Muller, Marisa Sophiea, Sabina Rinaldi, Antonio Agudo, Eric J Duell, Elisabete Weiderpass, Kim Overvad, Anne Tjønneland, Jytte Halkjaer, Marie-Christine Boutron-Ruault, Franck Carbonnel, Iris Cervenka, Heiner Boeing, Rudolf Kaaks, Tilman Kühn, Antonia Trichopoulou, Georgia Martimianaki, Anna Karakatsani, Valeria PalaDomenico Palli, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, Guri Skeie, Charlotta Rylander, María-Dolores Chirlaque López, Maria-Jose Sánchez, Eva Ardanaz, Sara Regnér, Tanja Stocks, 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

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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.

Original languageEnglish
Pages (from-to)929-942
Number of pages14
JournalInternational Journal of Cancer
Volume146
Issue number4
Early online date03 May 2019
DOIs
Publication statusPublished - 15 Feb 2020

Bibliographical note

© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Keywords

  • Anthropometry
  • Body Fat Distribution
  • Cohort Studies
  • Esophageal Neoplasms/classification
  • Europe/epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Reproductive History
  • Risk Factors
  • Stomach Neoplasms/classification

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    Sanikini, H., Muller, D. C., Sophiea, M., Rinaldi, S., Agudo, A., Duell, E. J., Weiderpass, E., Overvad, K., Tjønneland, A., Halkjaer, J., Boutron-Ruault, M-C., Carbonnel, F., Cervenka, I., Boeing, H., Kaaks, R., Kühn, T., Trichopoulou, A., Martimianaki, G., Karakatsani, A., ... Cross, A. J. (2020). 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. International Journal of Cancer, 146(4), 929-942. https://doi.org/10.1002/ijc.32386