A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH–AARP Diet and Health Study

Abstract

Objective Incidence of esophageal adenocarcinoma (EAC) has increased rapidly over the past forty years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. However, it remains unclear whether abdominal obesity is associated with esophageal and gastric adenocarcinoma. Design Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218,854 participants in the prospective NIH-AARP cohort. Results 253 incident EAC, 191 gastric cardia adenocarcinomas, and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric cardia adenocarcinoma risk (highest [≥35 kg/m2] versus referent [18.5–<25 kg/m2]; hazard ratio (HR) 95% confidence interval (95% CI); 2.11 (1.09–4.09) and 3.67 (2.00–6.71), respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk, (highest versus referent; HR (95% CI) 2.01 (1.35–3.00) and 2.22 (1.43–3.47), respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest versus referent; HR (95% CI) 1.81 (1.24–2.64)); persisted in patients with normal BMI (18.5–<25 kg/m2). Mutual adjustment of WHR and BMI attenuated both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia. Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI.

Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies

“…When sex-specific results were presented, respectively, and did not provide information for both genders, we first analyzed together for gastric cancer (weighted by the inverse of their variance) and then separately for males and females. When subtype-specific estimates were available and did not provide information for total gastric cancer (17,18,24,(33)(34)(35)(36), they were only included in the analysis of cardia and non-cardia cancers. When studies provided both total gastric cancer and subtype-specific estimates (21,37,38), they were included in the analysis for both total gastric cancer and subtypespecific estimates, respectively.…”

“…13]. Unfortunately, several large cohort studies were not included in this meta-analysis (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Moreover, the previous analysis did not explore the effect of important confounders (such as smoking, alcohol use, and physical activity) on the relationship of BMI and gastric cancer.…”

Obesity and Oesophageal Cancer

“…In this prospective study with measured anthropometry at baseline, general obesity represented by BMI as well as abdominal obesity represented by waist circumference or waist-to-hip ratio were strongly positively associated with risk of oesophageal adenocarcinoma. After mutual adjustment, BMI was no longer associated with oesophageal adenocarcinoma, whereas both waist circumference and waist-to-hip ratio remained strongly positively associated (RR 3.76, 95% CI higher risk of oesophageal adenocarcinoma [16], the association with abdominal obesity (waistto-hip ratio) was attenuated but not eliminated by simultaneous adjustment for BMI, while the association with BMI was only slightly attenuated. In a meta-analysis on the association between waist circumference and risk of oesophageal adenocarcinoma, five studies including findings from the NIH-AARP Study [16] and an earlier investigation of EPIC [17] were summarized [14].…”

Gastric Cardia Cancer: How Much Is It from Fat?

“…A report from Australia also supported the finding of increase in risk of GCA and EAC with increase in WC. They reported a HR of 1.46 (95 % CI 1.05-2.04) per 10 cm increase in WC for GCA and EAC in a cohort of around 41,000 people between the ages of 25 and 75 years observed over 11 years [6].…”

“…There is room for error even in studies that have selected patients based on standardized classifications. Various studies have used the International Statistical Classification of Diseases and Related Health Problems (ICD-9) and International Classification of Diseases for Oncology (ICD-O) codes [5][6][7]. Misclassification in the ICD-9 coding system could lead to incorrect estimation of cancer incidence (Table 1).…”