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.
Highlights
Esophageal cancer is the seventh most common and gastric cancer the fifth most common cancer worldwide, with an estimated 572,000 and 1,000,000 cases in 2018, respectively.[1]
Several anthropometric variables were positively associated with esophageal adenocarcinoma (EA) in both men and women (Tables 1 and 2), respectively, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR)
Comparing the baseline characteristics of included participants to those excluded from the analysis because they lacked dietary or lifestyle information, revealed no substantial differences between the two groups, except participants excluded were very slightly older than the included participants. In this large prospective study, abdominal obesity was positively associated with EA and gastric cardia (GC), while the findings for esophageal squamous cell carcinoma (ESCC) were less clear
Summary
Esophageal cancer is the seventh most common and gastric cancer the fifth most common cancer worldwide, with an estimated 572,000 and 1,000,000 cases in 2018, respectively.[1] These cancers are more common in men than in women and are becoming more prevalent in many regions of the world.[1] Esophageal cancer can be categorized histologically as esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) and these subtypes have distinct etiologies. Gastric cancers are predominantly adenocarcinomas but their etiology appears to differ depending on their location in the gastric cardia (GC) or gastric noncardia (GNC). Smoking and alcohol are well-known risk factors for ESCC, whereas gastroesophageal reflux disease (GERD), smoking and obesity are established risk factors for EA.[2] Smoking and obesity are thought to be risk factors for GC, while Helicobacter pylori infection and smoking are risk factors for GNC.[3]
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