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.
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Sanikini Harinakshi, Muller David C, Sophiea Marisa, Rinaldi Sabina, Agudo Antonio, Duell Eric J, Weiderpass Elisabete, Overvad Kim, Tjønneland Anne, Halkjaer Jytte, Boutron-Ruault Marie-Christine, Carbonnel Franck, Cervenka Iris, Boeing Heiner, Kaaks Rudolf, Kühn Tilman, Trichopoulou Antonia, Martimianaki Georgia, Karakatsani Anna, Pala Valeria, Palli Domenico, Mattiello Amalia, Tumino Rosario, Sacerdote Carlotta, Skeie Guri, Rylander Charlotta, Chirlaque López María-Dolores, Sánchez Maria-Jose, Ardanaz Eva, Regnér Sara, Stocks Tanja, Bueno-de-Mesquita Bas, Vermeulen Roel C H, Aune Dagfinn, Tong Tammy Y N, Kliemann Nathalie, Murphy Neil, Chadeau-Hyam Marc, Gunter Marc J, Cross Amanda J
Аннотация
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.