Abdominal obesity and the risk of esophageal and gastric cardia carcinomas.
ABSTRACT Esophageal adenocarcinoma is rapidly increasing in incidence. Body mass index (BMI) is a risk factor, but its distribution does not reflect the demographic distribution of the cancer (which is highest among White men). Abdominal obesity patterns may explain this discordance, but no studies exist to date.
Nested case-control study within 206,974 members of the Kaiser Permanente multiphasic health checkup cohort; subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of esophageal and cardia cancers using registry data.
101 incident esophageal adenocarcinomas, 105 cardia adenocarcinomas, and 144 esophageal squamous cell carcinomas were detected (BMI data available for all cases; abdominal measurements for a subset). Increasing abdominal diameter was strongly associated with an increased risk of esophageal adenocarcinoma [odds ratio (OR), 3.47; 95% confidence interval (95% CI), 1.29-9.33; abdominal diameter, > or =25 versus <20 cm]. Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.78; 95% CI, 1.14-20.11). The association was also not diminished by adjustment for gastroesophageal reflux-type symptoms, although reflux-type symptoms were separately associated with both abdominal diameter and cancer risk. Abdominal diameter was not associated with the risk of cardia adenocarcinomas (OR, 1.28; 95% CI, 0.38-4.25; diameter, > or =25 versus <20 cm) or esophageal squamous cell carcinomas (OR, 0.78; 95% CI, 0.32-1.92).
Increasing abdominal diameter was associated with an increased risk of esophageal adenocarcinoma, independent of BMI. Cancer risk was not substantially mediated through gastroesophageal reflux-type symptoms, although symptoms may imperfectly measure reflux severity. Given abdominal obesity is more common among males, these findings suggest that increases in obesity may disproportionately increase the risk of esophageal adenocarcinoma in males.
Article: Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.[show abstract] [hide abstract]
ABSTRACT: Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54-0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21-0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.International Journal of Cancer 12/2011; 129(11):2681-93. · 5.44 Impact Factor
Article: Prognostic impact of body mass index stratified by smoking status in patients with esophageal adenocarcinoma.[show abstract] [hide abstract]
ABSTRACT: Given that smoking affects body mass index (BMI) and survival, stratification by smoking status may be required to determine the true prognostic impact of BMI. Although obesity increases risk for developing esophageal adenocarcinoma (EAC), the prognostic influence of obesity and its potential modification by smoking status is unknown in this disease. All patients (N = 778) underwent potentially curative esophagectomy. BMI was calculated using measured height and weight at surgery and categorized as obese (≥ 30 kg/m(2)), overweight (25 to 29.9 kg/m(2)), or normal (18.5 to 24.9 kg/m(2)). Cigarette smoking was categorized as never or ever. The association of BMI with disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) was determined by Cox regression. Excess BMI was significantly associated with DSS in a manner that differed substantially by smoking status (P for interaction = .023). Among never smokers, obesity was significantly associated with adverse DSS (hazard ratio [HR] = 2.11; 95% CI, 1.31 to 3.43; P = .002), DFS (HR = 2.03; 95% CI, 1.30 to 3.18; P = .002), and OS (HR = 1.97; 95% CI, 1.24 to 3.14; P = .004), as compared with normal weight, after adjusting for covariates. By contrast, among ever smokers, obesity was not prognostic, and overweight status was significantly associated with favorable survival in univariate, but not multivariate, analysis. Obesity among never smokers was independently associated with two-fold worsening of DSS, DFS, and OS after surgery for EAC, after adjusting for known prognostic factors. These data, in one of the largest reported resected EAC cohorts, are the first to show an adverse prognostic impact of obesity in EAC.Journal of Clinical Oncology 12/2011; 29(34):4561-7. · 18.37 Impact Factor
Article: MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.[show abstract] [hide abstract]
ABSTRACT: Overweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.Molecular Carcinogenesis 11/2011; · 3.16 Impact Factor