Abstract
Background: Increasing meat intake and its possible role in the development of esophageal adenocarcinoma raises the question whether meat consumption is associated with the premalignant lesion, Barrett's esophagus.
Methods: Associations between the risk of Barrett's esophagus and meat consumption, intake of N-nitrosodimethylamine, nitrite, and heme iron were examined in the Netherlands Cohort Study among 120,852 subjects aged 55 to 69 years in 1986. Exposure was measured on the basis of a 150-item food frequency questionnaire. After 16.3 years of follow-up, 447 Barrett's esophagus cases with specialized intestinal metaplasia and 3,919 subcohort members were analyzed in a case-cohort design.
Results: There was no association of any of the examined exposures with Barrett's risk in men or women. Results were similar in age-adjusted and fully adjusted models and in models excluding the first two years of follow-up.
Conclusions: Our results do not support a role of meat consumption and N-nitrosation related factors in the development of Barrett's esophagus.
Impact: The possible causal association between red meat intake and esophageal adenocarcinoma is unlikely to be mediated by mechanisms through the development of Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 22(6); 1162–6. ©2013 AACR.
Introduction
Barrett's esophagus is a precursor of esophageal adenocarcinoma and its incidence is increasing (1). Components of diet are potentially important modifiable risk factors of esophageal adenocarcinoma and Barrett's esophagus. Meat intake has been rising in the developed world and there is few data on the associations between meat intake and the risk of Barrett's esophagus (2, 3).
N-nitroso compounds in processed meat and endogenously formed through nitrosation of amines via nitrite are thought to be partly explaining the associations between red and processed meats and esophageal cancer risk. It is unclear, however, whether N-nitroso compounds, or compounds that influence nitrosation, such as heme iron content of meat, may influence the risk of Barrett's esophagus.
Using prospective cohort data, we studied the association between meat and fish consumption, as well as the intake of N-nitrosodimethylamine (NDMA), nitrite, and heme iron and the risk of Barrett's esophagus.
Materials and Methods
The Netherlands cohort study (NLCS) was started in September 1986. At baseline 58,279 men and 62,573 women aged 55 to 69 years were recruited, and a self-administered questionnaire was completed by study participants (4). A case–cohort design was used for processing and analyzing data. The whole cohort was followed for 16.3 years for incident Barrett's cases by computerized record linkage to the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). Excerpts of all pathology records of cases were reviewed independently by a pathologist (A.L.C. Driessen) and a pathologist in training (C.J.R. Huysentruyt) who were blinded to exposure. Out of 974 cases, 371 were excluded on the basis of uncertain diagnosis, prevalent cancer, or Barrett's at baseline, esophageal, or gastric cancer diagnosed before or within half a year after Barrett's diagnosis, and because of inconsistent or missing data. In cases when histology was not specified initially, full pathology reports were retrieved and reviewed to identify the type of metaplasia. A total of 603 cases were available for analysis. Because of prevalent cancer or Barrett's at baseline and due to inconsistent or missing data, 1,081 subcohort members were excluded from further analysis.
Food and beverage consumption was assessed using a 150-item semiquantitative food frequency questionnaire that was validated against a 9-day diet record (5).
NDMA, nitrite, and heme iron intake was measured using questionnaire data as described previously (6).
Statistical analysis
Incidence rate ratios and 95% confidence intervals (CI) in men and women were estimated using Cox proportional hazards models. SEs were calculated using a robust variance estimator (7). The proportional hazard assumption was assessed using the scaled Schoenfeld residuals and by introducing time–covariate interactions into the models. Primary analysis was conducted using only cases with intestinal metaplasia (n = 447). Additional analyses were conducted using all cases and excluding the first 2 years of follow-up.
Results
Data from 249 men and 198 women cases with intestinal metaplasia and 3,919 subcohort members were available for analysis. Total meat intake in the subcohort was 105.5 (SD: 42.9) and 93.1 (SD: 39.4) g/day among men and women, respectively. Baseline use of nonsteroidal anti-inflammatory drug (NSAID) and lower esophageal sphincter relaxing medications was higher among cases than subcohort members (NSAID: 8% vs. 6% in men, and 12% vs. 8% in women; lower esophageal sphincte: 18% vs. 16% in men, and 17% vs. 14% in women). Dietary intakes were similar between cases and subcohort members.
No association was observed between meat consumption, NDMA, nitrite, and heme intake, and the risk of Barrett's esophagus among men (Table 1) and women (Table 2). Results were similar when cases with non–intestinal metaplasia were included and when the first 2 years of follow-up were excluded from the analysis (data not shown).
. | Subcohort . | . | . | ||
---|---|---|---|---|---|
. | No. of cases . | Person years . | Median intake (g/d) . | HRa (95% CI) . | HRb (95% CI) . |
Total meat intake | |||||
T1 | 93 | 8,768 | 70.9 | 1 | 1 |
T2 | 83 | 8,598 | 102.4 | 0.92 (0.67–1.27) | 0.93 (0.67–1.28) |
T3 | 73 | 9,051 | 145.1 | 0.76 (0.55–1.06) | 0.79 (0.56–1.13) |
Ptrend | 0.10 | 0.20 | |||
Continuous (50 g/d increment) | 0.91 (0.78–1.06) | 0.93 (0.79–1.10) | |||
Red meat intake | |||||
T1 | 93 | 8,771 | 57.9 | 1 | 1 |
T2 | 81 | 8,610 | 88.9 | 0.89 (0.65–1.23) | 0.91 (0.65–1.27) |
T3 | 75 | 9,035 | 129.3 | 0.78 (0.56–1.09) | 0.81 (0.57–1.14) |
Ptrend | 0.14 | 0.23 | |||
Continuous (50 g/d increment) | 0.92 (0.78–1.09) | 0.94 (0.79–1.13) | |||
Processed meat intake | |||||
T1 | 81 | 8,676 | 5.8 | 1 | 1 |
T2 | 89 | 8,788 | 17.2 | 1.10 (0.80–1.53) | 1.10 (0.79–1.54) |
T3 | 79 | 8,953 | 36.4 | 0.96 (0.69–1.35) | 1.01 (0.68–1.48) |
Ptrend | 0.74 | 0.97 | |||
Continuous (50 g/d increment) | 0.85 (0.60–1.22) | 0.91 (0.59–1.41) | |||
Poultry intake | |||||
T1 | 115 | 11,055 | 0.0 | 1 | 1 |
T2 | 57 | 6,682 | 13.2 | 0.83 (0.59–1.16) | 0.84 (0.59–1.19) |
T3 | 77 | 8,680 | 22.8 | 0.85 (0.63–1.16) | 0.89 (0.64–1.24) |
Ptrend | 0.27 | 0.43 | |||
Continuous (50 g/d increment) | 0.88 (0.52–1.48) | 0.93 (0.55–1.58) | |||
Fish intake | |||||
T1 | 102 | 10,544 | 0.0 | 1 | 1 |
T2 | 74 | 7,477 | 11.5 | 1.03 (0.75–1.42) | 1.09 (0.78–1.53) |
T3 | 73 | 8,396 | 25.5 | 0.91 (0.66–1.25) | 0.99 (0.70–1.41) |
Ptrend | 0.57 | 0.98 | |||
Continuous (50 g/d increment) | 0.87 (0.58–1.31) | 0.98 (0.64–1.49) | |||
NDMA intake | (ng/d) | ||||
T1 | 79 | 8,506 | 40.4 | 1 | 1 |
T2 | 94 | 8,962 | 83.9 | 1.14 (0.83–1.58) | 1.20 (0.85–1.68) |
T3 | 76 | 8,948 | 254.1 | 0.94 (0.67–1.32) | 1.01 (0.70–1.47) |
Ptrend | 0.47 | 0.73 | |||
Continuous (0.1 μg/d increment) | 0.97 (0.90–1.03) | 0.97 (0.90–1.04) | |||
Nitrite intake | (mg/d) | ||||
T1 | 86 | 8,643 | 0.03 | 1 | 1 |
T2 | 90 | 8,883 | 0.12 | 1.04 (0.75–1.43) | 1.04 (0.74–1.45) |
T3 | 73 | 8,890 | 0.28 | 0.84 (0.60–1.18) | 0.87 (0.60–1.26) |
Ptrend | 0.26 | 0.40 | |||
Continuous (0.1 mg/d increment) | 0.98 (0.89–1.08) | 1.00 (0.89–1.13) | |||
Heme iron intake | (mg/d) | ||||
T1 | 95 | 8,669 | 0.71 | 1 | 1 |
T2 | 83 | 8,923 | 1.09 | 0.85 (0.62–1.17) | 0.90 (0.64–1.26) |
T3 | 71 | 8,824 | 1.62 | 0.74 (0.53–1.02) | 0.79 (0.55–1.14) |
Ptrend | 0.07 | 0.22 | |||
Continuous (1 mg/d increment) | 0.87 (0.66–1.15) | 0.93 (0.68–1.27) |
. | Subcohort . | . | . | ||
---|---|---|---|---|---|
. | No. of cases . | Person years . | Median intake (g/d) . | HRa (95% CI) . | HRb (95% CI) . |
Total meat intake | |||||
T1 | 93 | 8,768 | 70.9 | 1 | 1 |
T2 | 83 | 8,598 | 102.4 | 0.92 (0.67–1.27) | 0.93 (0.67–1.28) |
T3 | 73 | 9,051 | 145.1 | 0.76 (0.55–1.06) | 0.79 (0.56–1.13) |
Ptrend | 0.10 | 0.20 | |||
Continuous (50 g/d increment) | 0.91 (0.78–1.06) | 0.93 (0.79–1.10) | |||
Red meat intake | |||||
T1 | 93 | 8,771 | 57.9 | 1 | 1 |
T2 | 81 | 8,610 | 88.9 | 0.89 (0.65–1.23) | 0.91 (0.65–1.27) |
T3 | 75 | 9,035 | 129.3 | 0.78 (0.56–1.09) | 0.81 (0.57–1.14) |
Ptrend | 0.14 | 0.23 | |||
Continuous (50 g/d increment) | 0.92 (0.78–1.09) | 0.94 (0.79–1.13) | |||
Processed meat intake | |||||
T1 | 81 | 8,676 | 5.8 | 1 | 1 |
T2 | 89 | 8,788 | 17.2 | 1.10 (0.80–1.53) | 1.10 (0.79–1.54) |
T3 | 79 | 8,953 | 36.4 | 0.96 (0.69–1.35) | 1.01 (0.68–1.48) |
Ptrend | 0.74 | 0.97 | |||
Continuous (50 g/d increment) | 0.85 (0.60–1.22) | 0.91 (0.59–1.41) | |||
Poultry intake | |||||
T1 | 115 | 11,055 | 0.0 | 1 | 1 |
T2 | 57 | 6,682 | 13.2 | 0.83 (0.59–1.16) | 0.84 (0.59–1.19) |
T3 | 77 | 8,680 | 22.8 | 0.85 (0.63–1.16) | 0.89 (0.64–1.24) |
Ptrend | 0.27 | 0.43 | |||
Continuous (50 g/d increment) | 0.88 (0.52–1.48) | 0.93 (0.55–1.58) | |||
Fish intake | |||||
T1 | 102 | 10,544 | 0.0 | 1 | 1 |
T2 | 74 | 7,477 | 11.5 | 1.03 (0.75–1.42) | 1.09 (0.78–1.53) |
T3 | 73 | 8,396 | 25.5 | 0.91 (0.66–1.25) | 0.99 (0.70–1.41) |
Ptrend | 0.57 | 0.98 | |||
Continuous (50 g/d increment) | 0.87 (0.58–1.31) | 0.98 (0.64–1.49) | |||
NDMA intake | (ng/d) | ||||
T1 | 79 | 8,506 | 40.4 | 1 | 1 |
T2 | 94 | 8,962 | 83.9 | 1.14 (0.83–1.58) | 1.20 (0.85–1.68) |
T3 | 76 | 8,948 | 254.1 | 0.94 (0.67–1.32) | 1.01 (0.70–1.47) |
Ptrend | 0.47 | 0.73 | |||
Continuous (0.1 μg/d increment) | 0.97 (0.90–1.03) | 0.97 (0.90–1.04) | |||
Nitrite intake | (mg/d) | ||||
T1 | 86 | 8,643 | 0.03 | 1 | 1 |
T2 | 90 | 8,883 | 0.12 | 1.04 (0.75–1.43) | 1.04 (0.74–1.45) |
T3 | 73 | 8,890 | 0.28 | 0.84 (0.60–1.18) | 0.87 (0.60–1.26) |
Ptrend | 0.26 | 0.40 | |||
Continuous (0.1 mg/d increment) | 0.98 (0.89–1.08) | 1.00 (0.89–1.13) | |||
Heme iron intake | (mg/d) | ||||
T1 | 95 | 8,669 | 0.71 | 1 | 1 |
T2 | 83 | 8,923 | 1.09 | 0.85 (0.62–1.17) | 0.90 (0.64–1.26) |
T3 | 71 | 8,824 | 1.62 | 0.74 (0.53–1.02) | 0.79 (0.55–1.14) |
Ptrend | 0.07 | 0.22 | |||
Continuous (1 mg/d increment) | 0.87 (0.66–1.15) | 0.93 (0.68–1.27) |
aAdjusted for age (years).
bAdjusted for age (years), smoking status (current vs. non-current smoker), years of cigarette smoking, number of cigarettes smoked per day, total energy intake (kjoules/day), body mass index (quintiles), vegetable intake (g/day), fruit intake (g/day), levels of education (4 categories), nonoccupational physical activity (4 categories), use of lower esophageal sphincter relaxing medications (yes/no), and alcoholic beverages not including beer for models of NDMA intake and alcohol intake for all other models (g/day).
Abbreviations: NDMA, N-nitrosodimethylamine; T, tertile.
. | Subcohort . | . | . | ||
---|---|---|---|---|---|
. | No. of cases . | Person years . | Median intake (g/d) . | HRa (95% CI) . | HRb (95% CI) . |
Total meat intake | |||||
T1 | 77 | 9,780 | 57.7 | 1 | 1 |
T2 | 65 | 9,940 | 91.9 | 0.83 (0.59–1.17) | 0.81 (0.57–1.16) |
T3 | 56 | 9,918 | 126.6 | 0.72 (0.50–1.03) | 0.72 (0.49–1.06) |
Ptrend | 0.07 | 0.09 | |||
Continuous (50 g/d increment) | 0.86 (0.71–1.04) | 0.84 (0.68–1.05) | |||
Red meat intake | |||||
T1 | 74 | 9,690 | 44.9 | 1 | 1 |
T2 | 66 | 10,094 | 77.9 | 0.86 (0.61–1.22) | 0.81 (0.57–1.16) |
T3 | 58 | 9,855 | 114.9 | 0.77 (0.54–1.11) | 0.77 (0.52–1.13) |
Ptrend | 0.17 | 0.19 | |||
Continuous (50 g/d increment) | 0.86 (0.70–1.06) | 0.85 (0.67–1.06) | |||
Processed meat intake | |||||
T1 | 66 | 9,892 | 3.6 | 1 | 1 |
T2 | 71 | 9,806 | 11.9 | 1.10 (0.77–1.56) | 1.07 (0.74–1.55) |
T3 | 61 | 9,940 | 25.6 | 0.94 (0.65–1.35) | 0.91 (0.62–1.34) |
Ptrend | 0.64 | 0.56 | |||
Continuous (50 g/d increment) | 0.92 (0.53–1.62) | 0.93 (0.50–1.74) | |||
Poultry intake | |||||
T1 | 98 | 13,309 | 0.0 | 1 | 1 |
T2 | 44 | 7,270 | 13.2 | 0.83 (0.57–1.20) | 0.81 (0.55–1.19) |
T3 | 56 | 9,060 | 22.8 | 0.84 (0.60–1.19) | 0.84 (0.58–1.20) |
Ptrend | 0.28 | 0.28 | |||
Continuous (50 g/d increment) | 0.89 (0.51–1.55) | 0.92 (0.52–1.63) | |||
Fish intake | |||||
T1 | 60 | 9,854 | 0.0 | 1 | 1 |
T2 | 79 | 10,253 | 7.9 | 1.28 (0.90–1.82) | 1.33 (0.92–1.92) |
T3 | 59 | 9,532 | 21.6 | 1.02 (0.70–1.48) | 1.13 (0.76–1.69) |
Ptrend | 0.90 | 0.68 | |||
Continuous (50 g/d increment) | 1.12 (0.67–1.89) | 1.28 (0.75–2.19) | |||
NDMA intake | (ng/d) | ||||
T1 | 59 | 9,843 | 26.5 | 1 | 1 |
T2 | 74 | 9,975 | 44.5 | 1.23 (0.86–1.77) | 1.30 (0.89–1.89) |
T3 | 65 | 9,820 | 74.8 | 1.12 (0.77–1.63) | 1.31 (0.87–1.96) |
Ptrend | 0.65 | 0.23 | |||
Continuous (0.1 μg/d increment) | 0.86 (0.67–1.09) | 0.92 (0.76–1.11) | |||
Nitrite intake | (mg/d) | ||||
T1 | 68 | 9,950 | 0.02 | 1 | 1 |
T2 | 73 | 10,008 | 0.08 | 1.07 (0.76–1.52) | 1.06 (0.73–1.53) |
T3 | 57 | 9,681 | 0.20 | 0.87 (0.60–1.26) | 0.86 (0.58–1.27) |
Ptrend | 0.38 | 0.36 | |||
Continuous (0.1 mg/d increment) | 0.97 (0.85–1.12) | 0.99 (0.84–1.15) | |||
Heme iron intake | (mg/d) | ||||
T1 | 79 | 9,861 | 0.56 | 1 | 1 |
T2 | 55 | 9,885 | 0.92 | 0.70 (0.49–1.00) | 0.69 (0.47–1.00) |
T3 | 64 | 9,893 | 1.32 | 0.81 (0.57–1.14) | 0.83 (0.57–1.21) |
Ptrend | 0.26 | 0.36 | |||
Continuous (1 mg/d increment) | 0.80 (0.59–1.08) | 0.80 (0.58–1.11) |
. | Subcohort . | . | . | ||
---|---|---|---|---|---|
. | No. of cases . | Person years . | Median intake (g/d) . | HRa (95% CI) . | HRb (95% CI) . |
Total meat intake | |||||
T1 | 77 | 9,780 | 57.7 | 1 | 1 |
T2 | 65 | 9,940 | 91.9 | 0.83 (0.59–1.17) | 0.81 (0.57–1.16) |
T3 | 56 | 9,918 | 126.6 | 0.72 (0.50–1.03) | 0.72 (0.49–1.06) |
Ptrend | 0.07 | 0.09 | |||
Continuous (50 g/d increment) | 0.86 (0.71–1.04) | 0.84 (0.68–1.05) | |||
Red meat intake | |||||
T1 | 74 | 9,690 | 44.9 | 1 | 1 |
T2 | 66 | 10,094 | 77.9 | 0.86 (0.61–1.22) | 0.81 (0.57–1.16) |
T3 | 58 | 9,855 | 114.9 | 0.77 (0.54–1.11) | 0.77 (0.52–1.13) |
Ptrend | 0.17 | 0.19 | |||
Continuous (50 g/d increment) | 0.86 (0.70–1.06) | 0.85 (0.67–1.06) | |||
Processed meat intake | |||||
T1 | 66 | 9,892 | 3.6 | 1 | 1 |
T2 | 71 | 9,806 | 11.9 | 1.10 (0.77–1.56) | 1.07 (0.74–1.55) |
T3 | 61 | 9,940 | 25.6 | 0.94 (0.65–1.35) | 0.91 (0.62–1.34) |
Ptrend | 0.64 | 0.56 | |||
Continuous (50 g/d increment) | 0.92 (0.53–1.62) | 0.93 (0.50–1.74) | |||
Poultry intake | |||||
T1 | 98 | 13,309 | 0.0 | 1 | 1 |
T2 | 44 | 7,270 | 13.2 | 0.83 (0.57–1.20) | 0.81 (0.55–1.19) |
T3 | 56 | 9,060 | 22.8 | 0.84 (0.60–1.19) | 0.84 (0.58–1.20) |
Ptrend | 0.28 | 0.28 | |||
Continuous (50 g/d increment) | 0.89 (0.51–1.55) | 0.92 (0.52–1.63) | |||
Fish intake | |||||
T1 | 60 | 9,854 | 0.0 | 1 | 1 |
T2 | 79 | 10,253 | 7.9 | 1.28 (0.90–1.82) | 1.33 (0.92–1.92) |
T3 | 59 | 9,532 | 21.6 | 1.02 (0.70–1.48) | 1.13 (0.76–1.69) |
Ptrend | 0.90 | 0.68 | |||
Continuous (50 g/d increment) | 1.12 (0.67–1.89) | 1.28 (0.75–2.19) | |||
NDMA intake | (ng/d) | ||||
T1 | 59 | 9,843 | 26.5 | 1 | 1 |
T2 | 74 | 9,975 | 44.5 | 1.23 (0.86–1.77) | 1.30 (0.89–1.89) |
T3 | 65 | 9,820 | 74.8 | 1.12 (0.77–1.63) | 1.31 (0.87–1.96) |
Ptrend | 0.65 | 0.23 | |||
Continuous (0.1 μg/d increment) | 0.86 (0.67–1.09) | 0.92 (0.76–1.11) | |||
Nitrite intake | (mg/d) | ||||
T1 | 68 | 9,950 | 0.02 | 1 | 1 |
T2 | 73 | 10,008 | 0.08 | 1.07 (0.76–1.52) | 1.06 (0.73–1.53) |
T3 | 57 | 9,681 | 0.20 | 0.87 (0.60–1.26) | 0.86 (0.58–1.27) |
Ptrend | 0.38 | 0.36 | |||
Continuous (0.1 mg/d increment) | 0.97 (0.85–1.12) | 0.99 (0.84–1.15) | |||
Heme iron intake | (mg/d) | ||||
T1 | 79 | 9,861 | 0.56 | 1 | 1 |
T2 | 55 | 9,885 | 0.92 | 0.70 (0.49–1.00) | 0.69 (0.47–1.00) |
T3 | 64 | 9,893 | 1.32 | 0.81 (0.57–1.14) | 0.83 (0.57–1.21) |
Ptrend | 0.26 | 0.36 | |||
Continuous (1 mg/d increment) | 0.80 (0.59–1.08) | 0.80 (0.58–1.11) |
aadjusted for age (years).
badjusted for age (years), smoking status (current vs. non-current smoker), years of cigarette smoking, number of cigarettes smoked per day, total energy intake (kjoules/day), body mass index (quintiles), vegetable intake (g/day), fruit intake (g/day), levels of education (4 categories), nonoccupational physical activity (4 categories), use of lower esophageal sphincter relaxing medications (yes/no), and alcoholic beverages not including beer for models of NDMA intake and alcohol intake for all other models (g/day).
Abbreviations: NDMA, N-nitrosodimethylamine; T, tertile.
Discussion
This is the first cohort study examining the association between meat intake, N-nitrosation–related intakes, and the risk of Barrett's esophagus. Data from epidemiologic studies investigating associations between meat consumption and Barrett's esophagus is limited. Lack of association with meat intake found in this study is in line with a case–control study conducted in Ireland (3). Another case-control study found an inverse relationship between total meat intake and long-segment Barrett's esophagus risk (2), but different types of meat were not assessed in this study.
Strengths of our study include its prospective design, the large number of cases, and the use of full pathology reports to evaluate the type of metaplasia. The lack of information on gastroesophageal reflux and meat cooking methods are limitations of the study, and we cannot rule out confounding effect of these factors. Our study also assumes that cohort members not diagnosed with Barrett's disease are disease free. However, Barrett's diagnosis has also been made in asymptomatic individuals (8); therefore we may have missed cases in our cohort.
In summary, our results do not support a role of meat intake in the etiology of Barrett's esophagus and suggest that the association between red meat intake and esophageal adenocarcinoma, if causal, is explained by mechanisms other than through the development of Barrett's esophagus.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Authors' Contributions
Conception and design: L.J. Schouten, P.A. van den Brandt
Development of methodology: A.P. Keszei, P.A. van den Brandt
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): A.P. Keszei, L.J. Schouten, A.L.C. Driessen, C.J.R. Huysentruyt, P.A. van den Brandt
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): A.P. Keszei, C.J.R. Huysentruyt, P.A. van den Brandt
Writing, review, and/or revision of the manuscript: A.P. Keszei, L.J. Schouten, A.L.C. Driessen, C.J.R. Huysentruyt, Y.C.A. Keulemans, P.A. van den Brandt
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): L.J. Schouten
Study supervision: P.A. van den Brandt
Acknowledgments
The authors thank PALGA and the pathologist for supplying the pathology reports of Barrett's cases. The authors also thank Drs. A. Volovics and A. Kester for statistical advice; S. van de Crommert, H. Brants, J. Nelissen, C. de Zwart, M. Moll, W. van Dijk, M. Jansen, Ellen Dutman, and A. Pisters for assistance; and H. van Montfort, T. van Moergastel, L. van den Bosch, and R. Schmeitz for programming assistance.
Grant Support
This study was financially supported by a grant from Maag Lever Darm Stichting (MLDS; WO 09-53).