Adenocarcinoma of the oesophagus and gastric cardia: Male preponderance in association with obesity

doi:10.1016/j.ejca.2005.12.024

European Journal of Cancer

Volume 42, Issue 8, May 2006, Pages 1151-1158

https://doi.org/10.1016/j.ejca.2005.12.024 Get rights and content

Abstract

Recent evidence links obesity with the rising incidence of oesophageal adenocarcinoma. In Ireland between 1995 and 2004 the incidence of oesophageal adenocarcinoma increased by 38%, and this coincided with a 67% increase in the prevalence of obesity. In this study, a prospective case-control study was undertaken in 760 patients presenting to a tertiary centre between 1994 and 2004 diagnosed with cancer of the oesophagus, gastric cardia or stomach. Data were compared with 893 healthy controls. Multivariate logistic regression models were used to calculate the odds ratio (OR) of developing either cancer type according to quartiles of body mass index (BMI). Based on pre-illness BMI, 82% of patients who developed adenocarcinoma of the oesophagus were either overweight or obese compared with 59% of the healthy control population (P < 0.001). A dose-dependent relationship existed between BMI and oesophageal adenocarcinoma in males. The adjusted odds ratio was 4.3 (95% CI: 2.3–7.9) among males in the highest BMI quartile compared with males in the lowest quartile (P < 0.001 for trend). Using common cut-off points for BMI, the OR of adenocarcinoma of the lower oesophagus was 11.3 times higher (95% CI: 3.5–36.4) for individuals with a BMI >30 kg/m² versus individuals with a BMI <22 kg/m² (P < 0.001 for trend). For adenocarcinoma of the gastric cardia, males in the top quartile of BMI had an OR of 3.5 (95% CI: 1.3–9.4) compared with the lowest quartile (P = 0.03 for trend). A significant (P < 0.001) inverse relationship between BMI and oesophageal SCC was observed.

The odds ratio for adenocarcinoma of the oesophagus, the oesophago-gastric junction and gastric cardia rose significantly with increasing BMI. For tumours of the lower oesophagus, obesity increased the risk 10.9-fold. The increased risk is significant in males only.

Introduction

The patterns of oesophageal cancer in Europe and North America are changing rapidly. The incidence of oesophageal adenocarcinoma is increasing by 5–10% per year.¹ The striking increased trends seen in adenocarcinoma of the oesophagus and gastric cardia are thought to result from several modifiable and interrelated risk factors, including chronic gastro-oesophageal reflux disease, poor diet, H. pylori eradication, and obesity.1, 2, 3 A recent study of population attributable risks for oesophageal adenocarcinoma linked being overweight to 41% of cases.³

The Republic of Ireland has witnessed a marked increase in the prevalence of obesity since the early 1990s, and 67% of men and 75% of women over the age of 51 are now overweight or obese.⁴ During this same period there was a 38% increase in the number of cases of oesophageal adenocarcinoma registered by the National Cancer Registry of Ireland.⁵ The incidence rate of oesophageal cancer in Ireland is amongst the highest in the western world with 11.7 cases per 100 000 males and 6.1 cases per 100 000 females compared with a European Union average of 9.5/100 000 for males and 2.2/100 000 for females.⁵ The aim of this study was to examine the impact of Body Mass Index (BMI) and obesity on the risk of upper gastrointestinal cancer in Irish subjects.

Section snippets

Patients and methods

All histologically confirmed cases of adenocarcinoma and squamous cell carcinoma (SCC) of the oesophagus, oesophago-gastric junction, gastric cardia, and stomach, diagnosed or treated at the Oesophageal Unit of St. James’s Hospital, Dublin between 1994 and 2004 were included. This Unit treats approximately 35% of patients in the Republic of Ireland with tumours at these sites, and approximately 50% of referrals can be treated with curative intent.

The tumour location was based on endoscopic and

Results

The sample population consisted of 239 females and 521 males, 508 patients had adenocarcinoma and 252 had SCC of the oesophagus. Tumour sites were lower oesophagus (n = 279), mid oesophagus (n = 91), oesophago-gastric junction (n = 142), upper oesophagus (n = 26), gastric cardia (n = 65), and fundus, body or distal stomach (n = 157).

Discussion

This study of an Irish population firmly supports the link between rising BMI and the risk of both adenocarcinoma of the oesophagus and gastric cardia. Obesity (BMI >30 kg/m²) was associated with a 4-fold risk of adenocarcinoma of the oesophagus compared with males and females with a normal BMI. When the analysis was split for individual tumour sites the risks associated with high BMI were strikingly more marked for males compared with females. Males with a BMI in the top quartile had an OR of

Conflict of interest statement

None declared.

Acknowledgements

The authors are grateful to Professor Michael Gibney and Dr. Sinead Mc Carthy of the Irish Universities Nutrition Alliance (IUNA), Trinity College Dublin, for allowing access to raw BMI data of healthy controls that took part in the North/South Ireland National Food Consumption Survey.

References (26)

A. Misra et al.
Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue deposits
Nutrition
(2003)
L.J. Wilson et al.
Association of obesity with hiatus hernia and esophagitis
Am J Gastroenterol
(1999)
P. Somasundar et al.
Differential effects of leptin on cancer in vitro
J Surg Res
(2003)
V. Flood et al.
Use of self-report to monitor overweight and obesity in populations: some issues for consideration
Aust N Z J Pub Health
(2000)
M.F. Kuczmarski et al.
Effects of age on validity of self-reported height, weight, and body mass index: findings from the Third National Health and Nutrition Examination Survey, 1988–1994
J Am Diet Assoc
(2001)
P.C. Enzinger et al.
Oesophageal cancer
N Engl J Med
(2003)
L.S. Engel et al.
Population attributable risks of oesophageal and gastric cancers
J Natl Cancer Inst Sep
(2003)
W.H. Chow et al.
An inverse relationship between cagA + strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma
Cancer Res
(1998)
S.N. McCarthy et al.
Irish universities nutrition alliance. Overweight, obesity and physical activity levels in Irish adults: evidence from the North/South Ireland food consumption survey
Proc Nutr Soc
(2002)
National Cancer Registry of Ireland. Available from:...

World Health Organisation consultation on obesity. Preventing and managing the global epidemic: Report of a WHO...

J.R. Siewert et al.

Classification of adenocarcinoma of the oesophago–gastric junction

Br J Surg

(1998)

S.S. Devesa et al.

Changing patterns in the incidence of oesophageal and gastric carcinoma in the United States

Cancer

(1998)

Cited by (76)

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study
2023, The Lancet Gastroenterology and Hepatology
Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy.
For this multicohort prospective study, we enrolled participants aged 40–75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed.
Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, –0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification.
We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals.
Science and Technology Commission of Shanghai Municipality.
The complexity of cancer origins at the gastro-oesophageal junction
2021, Best Practice and Research: Clinical Gastroenterology
Chronic acid-biliary reflux and Helicobacter pylori infection are instrumental environmental drivers of cancer initiation and progression in the upper gastrointestinal tract. Remarkably, although these environmental carcinogens are quite dissimilar, the tumour progression cascade these carcinogens engender is highly comparable. For this reason, studies of malignant progression occurring at the anatomic borderland between the oesophagus and the stomach have traditionally lumped junctional adenocarcinomas with either oesophageal adenocarcinoma or gastric adenocarcinoma. Whilst studies have revealed remarkable epidemiological and genetic similarities of these cancers and their associated premalignant conditions, these works have also revealed some key differences. This highlights that further scientific effort demands a dedicated focus on the understanding of the cell-cell interaction between the epithelium and the local microenvironment in this anatomic region. We here review available evidence with regards to tumour progression occurring at the gastro-oesophageal junction and contrast it with available data on cancer evolution in the metaplastic oesophagus and distal stomach.
Body mass index and risk of upper gastrointestinal cancer: A 30-year follow-up of the Linxian dysplasia nutrition intervention trial cohort
2020, Cancer Epidemiology
Although a number of previous studies have noted the association between body mass index (BMI) and upper gastrointestinal (UGI) cancer risk, little evidence exists in the Chinese esophageal squamous dysplasia population. This prospective study investigated the association between BMI and UGI cancer risk in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.
A total of 3298 participants were included in the final analysis. Asian-specific BMI cut-offs were used to define BMI subgroups: underweight <18.5 kg/m², normal ≥18.5 to <24 kg/m² and overweight or obese ≥24 kg/m². Hazard ratios (HRs) and 95 % confidence intervals (95 %CIs) were estimated using the Cox proportional hazard model.
During over 30 years of follow-up we identified 654 incident esophageal squamous-cell carcinoma (ESCC) cases and 434 gastric cancer cases which included 88 gastric non-cardia carcinoma (GNCC) and 346 gastric cardia carcinoma (GCC) cases. Relative to normal weight, overweight or obesity were associated with a significantly reduced risk of ESCC (HR 0.69, 95 %CI 0.48–0.98) after multivariate adjustment, including age at baseline, gender, smoking, drinking, family history of cancer, education and consumption of fresh fruit. Subgroup analyses found that clear effects were evident in women and subjects with a family history of cancer. No association with gastric cancer was observed in any subjects or subgroups.
Overweight/obesity was associated with decreased risk of ESCC in this dysplasia population, particularly in women and persons who had a family history of cancer. Future studies are needed to confirm these findings.
Changes of body mass index and body shape in relation to risk of gastric cancer: A population-based case-control study
2021, Journal of Cancer
Background: The results of previous studies are heterogeneous about the effect of body fatness on risk of gastric cancer (GC). Herein we investigated the effect of changes of BMI and body shape on risk of GC.
Methods: A population-based case-control study enrolled 1989 controls and 937 GC cases. Logistic regression models were used to calculate odd ratios (ORs) and 95% confidence intervals (CIs) for BMI and body shape in association with GC risk, according to anatomical subsite, Laurén's classification, sex and Helicobacter pylori (Hp) infection.
Results: Subjects with higher BMI or body shape 10 years before interview had a lower risk of GC regardless of anatomical subsite, Laurén's classification, and sex (all P for trend <0.05). But the relative risk patterns were different by Hp status. When checking the effect of changes of body fatness, in Hp+ stratum, the ORs (95% CI) were 0.40 (0.17-0.93) for subjects who were underweight at age 20 but had increased BMI afterwards, and 0.48 (0.32-0.73) for those of body shape 1/2 at age 20 but increased body shape subsequently, compared to subjects with stable BMI or body shape. When subjects had a normal BMI or 3/4 body shape at age 20, weight loss nearly doubled the risk of GC, and weight gain would decrease the risk.
Conclusion: The association between body fatness and GC risk might differ by time point of measurement and Hp-infection status. Further, the influence of changes of body fatness might be different by baseline body fatness and Hp-infection status.
Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990–2019
2024, Thoracic Cancer
Obesity, Dietary Fats, and Gastrointestinal Cancer Risk-Potential Mechanisms Relating to Lipid Metabolism and Inflammation
2024, Metabolites

View all citing articles on Scopus

View full text

Adenocarcinoma of the oesophagus and gastric cardia: Male preponderance in association with obesity

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Conflict of interest statement

Acknowledgements

Nutrition

Am J Gastroenterol

J Surg Res

Aust N Z J Pub Health

J Am Diet Assoc

Oesophageal cancer

N Engl J Med

Population attributable risks of oesophageal and gastric cancers

J Natl Cancer Inst Sep

An inverse relationship between cagA + strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma

Cancer Res

Irish universities nutrition alliance. Overweight, obesity and physical activity levels in Irish adults: evidence from the North/South Ireland food consumption survey

Proc Nutr Soc

Classification of adenocarcinoma of the oesophago–gastric junction

Br J Surg

Changing patterns in the incidence of oesophageal and gastric carcinoma in the United States

Cancer