Open Access Research article

Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580 000 subjects within the Me-Can project

Björn Lindkvist114*, Dorthe Johansen2, Tanja Stocks3, Hans Concin4, Tone Bjørge56, Martin Almquist7, Christel Häggström3, Anders Engeland56, Göran Hallmans8, Gabriele Nagel9, Håkan Jonsson10, Randi Selmer6, Hanno Ulmer11, Steinar Tretli12, Pär Stattin3 and Jonas Manjer132

Author Affiliations

1 Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

2 Department of Surgery, Skåne University Hospital, Malmö and Lund University, Malmö, Sweden

3 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden

4 Agency for Preventive and Social Medicine, Bregenz, Austria

5 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway

6 Norwegian Institute of Public Health, Oslo/Bergen, Norway

7 Department of Surgery, Skåne University Hospital, Lund and Lund University, Lund, Sweden

8 Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden

9 Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany

10 Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

11 Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria

12 Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway

13 The Malmö Diet and Cancer Study, Skåne University Hospital, Malmö, Sweden

14 Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden

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BMC Cancer 2014, 14:103  doi:10.1186/1471-2407-14-103

Published: 18 February 2014



Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study.


The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox’s proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS).


In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC.


In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.

Esophageal cancer; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Obesity; Hypertension