A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma

doi:10.1016/j.ejca.2007.12.009

European Journal of Cancer

Volume 44, Issue 3, February 2008, Pages 465-471

https://doi.org/10.1016/j.ejca.2007.12.009 Get rights and content

Abstract

The incidence of oesophageal adenocarcinoma (EADC) is rapidly increasing in Western countries and obesity is thought to be a major risk factor. We examined the association between BMI and EADC, gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma in a cohort of approximately 500,000 people in the United States (US). We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) with control for many potential confounders. We found that compared to people with a BMI of 18.5–25 kg/m², a BMI ⩾35 was associated with significantly increased risk of EADC, HR (95% CI) = 2.27 (1.44–3.59) and gastric cardia adenocarcinoma 2.46 (1.60–3.80), but not gastric non-cardia adenocarcinoma 0.84 (0.50–1.42). Using non-linear models, we found that higher BMI was associated with increased risk of EADC even within the normal BMI. Increased adiposity was associated with higher risk of EADC even within the normal weight range.

Introduction

In 1991, Blot et al. noted a precipitous increase in the incidence of oesophageal adenocarcinoma (EADC) in the United States.¹ Later updates from SEER² and from other cancer registries suggest that EADC rates have increased in many parts of the Western world.³ Unfortunately, most patients with oesophageal cancer do not come to medical attention until the tumour has reached an advanced stage and therapy with curative intent is impossible.⁴

Gastric cardia adenocarcinoma incidence rates are also increasing in the United States (US),¹ however the trend is not as sharp as with EADC. It is possible that some of this increase may be due to better subsite classification for gastric tumours rather than a true increase in incidence rates.⁵ Furthermore, most EADC and all gastric cardia adenocarcinomas occur near the gastro-oesophageal junction and may overgrow the junction, so pinpointing the site of tumour origin may not be possible. No current pathological, immunohistochemical or molecular techniques can accurately separate these two tumours, so misclassification does occur⁶ and some authors have suggested that the clinical, epidemiological, pathological and molecular features are similar enough that they may represent a single disease.⁷

Previous research on the association between BMI and EADC and gastric cardia adenocarcinoma has relied almost exclusively on case–control studies,8, 9, 10, 11, 12, 13 because the low incidence rates have precluded accruing sufficient case numbers in most cohorts. To our knowledge, only three prospective studies have examined the association.14, 15, 16 Two of these studies could not control for important potential confounders,¹⁴ such as cigarette smoking, and the other two had incomplete information on confounders.15, 16 All these studies have also relied primarily on categorical analyses of BMI and estimated the risks associated with being overweight or obese.¹²

Here, we prospectively examine the association between BMI and EADC, gastric cardia adenocarcinoma, and gastric non-cardia adenocarcinoma using the NIH-AARP Diet and Health Study cohort that has extensive information on potential confounders.

Section snippets

Study population

The establishment and recruitment procedures of the NIH-AARP Diet and Health study have been described.¹⁷ Briefly, between 1995 and 1996, a questionnaire eliciting information on demographic characteristics, dietary intake and health-related behaviours was mailed to 3.5 million AARP members. These members resided in six US states (California, Florida, Louisiana, New Jersey, North Carolina and Pennsylvania) and two metropolitan areas (Atlanta, Georgia and Detroit, Michigan) and were between 50

Results

Table 1 presents the cohort characteristics by BMI category. Less than 1% of the cohort had a BMI <18.5, and 35% of the cohort had a normal BMI between 18.5 and 25 at the time of the baseline interview. 43% of the cohort was overweight, 16% was obese and 6% were extremely obese, with a BMI over 35. Subjects with higher BMI were younger and had fewer years of education, smoked less, drank less alcohol and had less physical activity.

Table 2 presents both age and sex, and multivariate-adjusted

Discussion

We found a strong monotonically increasing association between BMI and the risk of oesophageal adenocarcinoma; compared to subjects with a normal BMI of 18.5–25, we saw significantly and progressively increased risk for subjects in BMI categories of 25–<30, 30–<35 and ⩾35. For gastric cardia adenocarcinoma, compared to our referent group, there was no increased risk for subjects with a BMI of 25–<30, but risk was significantly increased in subjects with BMIs of 30–<35 and for those with a BMI

Conflict of interest statement

None declared.

Acknowledgements

This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance

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A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma

Abstract

Introduction

Section snippets

Study population

Results

Discussion

Conflict of interest statement

Acknowledgements

Eur J Cancer

Rising incidence of adenocarcinoma of the oesophagus and gastric cardia

JAMA

The role of overdiagnosis and reclassification in the marked increase of oesophageal adenocarcinoma incidence

J Natl Cancer Inst

Demographic variations in the rising incidence of esophageal adenocarcinoma in white males

Cancer

Esophageal cancer

New Engl J Med

Influence of site classification on cancer incidence rates: an analysis of gastric cardia carcinomas

J Natl Cancer Inst

Disparities in the classification of esophageal and cardia adenocarcinomas and their influence on reported incidence rates

Ann Surg

Three different subsite classification systems for carcinomas in the proximity of the GEJ, but is it all one disease?

J Gastroenterol Hepatol

Association between body mass and adenocarcinoma of the esophagus and gastric cardia

Ann Intern Med

A case–control study of oesophageal adenocarcinoma in women: a preventable disease

Br J Cancer

Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia

J Natl Cancer Inst

Adenocarcinoma of the esophagus: role of obesity and diet

J Natl Cancer Inst

Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis

Cancer Epidemiol Biomarkers Prev