Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium

Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA, Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD, USA, Queensland Institute of Medical Research, Brisbane, Australia, School of Population Health, University of Queensland, Brisbane, Australia, Division of Cancer Etiology, Department of Population Sciences, City of Hope, Duarte, CA, USA, RTI International, Rockville, MD, USA, Department of Epidemiology and Public Health, Yale University School of Public Health, New Haven, CT, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, National Cancer Registry Ireland, Cork, Ireland, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA, Department of Surgery and the Genomic Medicine and Pathobiology Group, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, Centre for Public Health, Queen's University, Belfast, Northern Ireland, Division of Research and Oakland Medical Center, Kaiser Permanente, Northern California, Oakland, CA, USA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA and Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC, USA.
International Journal of Epidemiology (Impact Factor: 9.18). 11/2012; 41(6). DOI: 10.1093/ije/dys176
Source: PubMed


Background Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms.
Methods Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m2) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender.
Results The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI ≥40 was associated with both OA (OR 4.76, 95% CI 2.96–7.66) and OGJA (OR 3.07, 95% CI 1.89–4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk.
Conclusions These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.

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Available from: Linda Sharp, Jan 31, 2014
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    • "However, in addition to those variables included in the minimally adjusted models, we included the following covariates in all study-specific maximally adjusted models given previous evidence of associations between these exposures and adenocarcinomas of the esophagus: BMI (categorical: <25, 25–29.9, ≥30) [18], education (study-specific) [19], [20], alcohol consumption (categorical: <7, 7–20, ≥21 drinks per week) [21], and cigarette smoking (categorical: 0, 1–14, 15–29, 30–44, ≥45 pack-years) [13]. Results were not materially different between minimally and maximally adjusted models, thus we present only the latter results. "
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    ABSTRACT: Background Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. Conclusions This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
    PLoS ONE 07/2014; 9(7):e103508. DOI:10.1371/journal.pone.0103508 · 3.23 Impact Factor
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    • "Moreover, the extended number of physical activity exposures we were able to assess also does not provide any evidence for an association with risk of EA. All previous analyses, including this AARP analysis, adjusted for BMI as this may be considered a potential confounder given its association with physical activity [25] as well as EA [26]. The predominant causal theory for the positive association between BMI with EA is that obesity increases the propensity for acid reflux via increasing intra-gastric pressure [27], distorting the lower esophageal sphincter [28,29], and increasing the likelihood for hiatal hernia [29,30]. "
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    ABSTRACT: Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI). During 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR >5 times/week vs. never =0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15-18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR 5-6 hrs/day vs. <1 hr =0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. We find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior.
    PLoS ONE 12/2013; 8(12):e84805. DOI:10.1371/journal.pone.0084805 · 3.23 Impact Factor
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    ABSTRACT: Oesophageal adenocarcinoma will soon cease to be a rare form of cancer for people born after 1940. In many Western countries, its incidence has increased more rapidly than other digestive cancers. Incidence started increasing in the Seventies in England and USA, 15 years later in Western Europe and Australia. The cumulative risk between the ages of 15 and 74 is particularly striking in the UK, with a tenfold increase in men and fivefold increase in women in little more than a single generation. Prognosis is poor with a 5-year relative survival rate of less than 10%. The main known risk factors are gastro-oesophageal reflux, obesity (predominantly mediated by intra-abdominal adipose tissues) and smoking. Barrett's oesophagus is a precancerous lesion, however, the risk of degeneration has been overestimated. In population-based studies the annual risk of adenocarcinoma varied between 0.12% and 0.14% and its incidence between 1.2 and 1.4 per 1000 person-years. Only 5% of subjects with Barrett's oesophagus die of oesophageal adenocarcinoma. On the basis of recent epidemiological data, new surveillance strategies should be developed. The purpose of this review is to focus on the epidemiology and risk factors of oesophageal adenocarcinoma.
    Digestive and Liver Disease 02/2013; 45(8). DOI:10.1016/j.dld.2012.12.020 · 2.96 Impact Factor
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