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

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.

Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort

“…reproductive factors in women and oesophageal squamous cell carcinoma, ever having a still birth/miscarriage/termination was positively associated with this malignancy and an older age at first live birth and last live birth was inversely associated. Our study found a positive association between BMI and oesophageal adenocarcinoma among men, which is in line with previous cohort studies [32,33], but we found no statistically significant association for women, which is inconsistent with data from the Million Women's Study and the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort [34,35]. However, we had very few cases of oesophageal adenocarcinoma among women in this study (n = 48) and the test for interaction by sex was not statistically significant.…”

“…After adjustment for waist-to-hip ratio, the positive association between BMI and oesophageal adenocarcinoma in men was attenuated but remained statistically significant. The NIH-AARP study and EPIC study showed a non-significant positive association between BMI and oesophageal adenocarcinoma adjusted for waist-to-hip ratio [35,36]. Our study found a statistically significant positive association for gastric cardia cancer with BMI in men, but this association attenuated after adjustment for waist-to-hip ratio.…”

“…Our study found a statistically significant positive association for gastric cardia cancer with BMI in men, but this association attenuated after adjustment for waist-to-hip ratio. The NIH-AARP study showed a significant positive association for gastric cardia cancer with BMI (HR 3.28, 95% CI: 1.76-6.11 for BMI �35 vs 18.5-<25) independently of waist-to-hip ratio [36], while the EPIC study showed no association between BMI and gastric cardia cancer [35]. In our study, analyses of body fat Table 6.…”

“…Our study found a statistically significant positive association for gastric cardia cancer with BMI in men, but this association attenuated after adjustment for waist-to-hip ratio. The NIH-AARP study showed a significant positive association for gastric cardia cancer with BMI (HR 3.28, 95% CI: 1.76–6.11 for BMI ≥35 vs 18.5-<25) independently of waist-to-hip ratio [ 36 ], while the EPIC study showed no association between BMI and gastric cardia cancer [ 35 ]. In our study, analyses of body fat percentage and oesophageal adenocarcinoma revealed similar results to those observed for BMI, with only a positive association evident for oesophageal adenocarcinoma in men, while no statistically significant association was observed for gastric cardia cancer and body fat percentage in men or women.…”

“…Furthermore, a positive association was observed between hip circumference and oesophageal adenocarcinoma in men, but this association attenuated after adjustment for waist circumference. Recent findings from the EPIC study analysis reported positive associations for oesophageal adenocarcinoma with waist circumference, and waist-to-hip ratio in both men and women independently of hip circumference and BMI [ 35 ].…”