Metabolic syndrome and esophageal and gastric cancer

Abstract

Background The role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear. Methods This was a large nationwide cohort study based on data from 11 prospective population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trøndelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low highdensity lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. Result Among 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95 % CI 1.14-1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95 % CI 0.77-2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95 % CI 0.64-1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48,. No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95 % CI 1.05-2.80), hypertension (HR 2.41, 95 % CI 1.44-4.03) and non-fasting glucose (HR 1.74, 95 % CI 1.18-2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men. Conclusion Metabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma.

Abdominal Obesity and Gastroesophageal Cancer Risk: Systematic Review and Meta-Analysis of Prospective Studies

“…Comparison of the highest category of WC with the lowest category revealed significant associations between higher WC and increased risk of total gastroesophageal cancer (RR: 1.68, 95% CI: 1.38, 2.04), GC (RR: 1.48, 95% CI: 1.24, 1.78), and esophageal cancer (RR: 2.06, 95% CI: 1.30, 3.24) (Figure 2 (Figure 3). Analysis restricted to two studies [27,28] sensitivity analyses that omitted one study at a time and calculated the combined RR for the remaining studies yielded consistent results. No evidence of publication bias was observed across studies (Begg, P>0.1; Egger, P>0.1).…”

“…Furthermore, six studies [36][37][38][39][40][41] were excluded because the risk estimate for the association of interest was not available. Finally, seven prospective cohort studies [24][25][26][27][28][29] -one publication [28] included two separate cohorts -from six publications were included in the final analysis. The characteristics of the included studies are summarised and listed in Table 1.…”

“…A total of 2130 gastroesophageal cancer cases were diagnosed amongst 913182 participants. Two prospective cohort studies were conducted in the United States [25,26] and Norway [28], and one each in Australia [24], multiple European countries [27], and China [29]. Regarding the sex of the participants, one study [29] evaluated only women and the remaining six [24][25][26][27][28] included both sexes.…”

“…Five prospective cohort studies [24,25,27,28] were eligible for the analysis of WC. Comparison of the highest category of WC with the lowest category revealed significant associations between higher WC and increased risk of total gastroesophageal cancer (RR: 1.68, 95% CI: 1.38, 2.04), GC (RR: 1.48, 95% CI: 1.24, 1.78), and esophageal cancer (RR: 2.06, 95% CI: 1.30, 3.24) (Figure 2 (Figure 3).…”

“…In addition, intra-abdominal fat has been hypothesised to be biologically different from fat in other areas with regard to tumor angiogenesis and cell proliferation [22,23]. Although general obesity has emerged as a potential risk factor for gastroesophageal cancer, but the association between abdominal obesity and gastroesophageal cancer is still poorly understood, partly because of sparse evidence from prospective studies available at that time, which limited the strength of the conclusions [24][25][26][27][28][29]. Given these considerations, providing clear evidence regarding potentially detrimental effect of abdominal obesity on gastroesophageal cancer would be important for clinical interventions, including weight loss program or weight management program and gastroesophageal cancer screening guidelines for obese individuals.…”