Alcohol and the Risk of Barrett Esophagus
In this large pooled analysis, alcohol consumption was not a risk factor for Barrett's esophagus. Compared with controls, average daily consumption of alcohol was moderately lower among cases; however, we found no consistent statistically significant association between alcohol consumption and the risk of Barrett's esophagus, and there was no evidence for a dose–response relationship. In beverage-specific analyses adjusted for total alcohol consumption, wine was associated with a moderately reduced risk of Barrett's esophagus. The association between alcohol and Barrett's esophagus was not modified by other factors (including sex, BMI, GERD, and smoking).
Previous studies have reported associations between alcohol and the risk of Barrett's esophagus; however, results have been conflicting. One possible explanation for the conflicting findings may be that individual studies have inadequate power to assess this association and are prone to type II error. Summarizing these results into an overall risk estimate using only published data is difficult given the different exposure categories, confounders, and analyses used in the published manuscripts. By contrast, in this study, we had access to individual participant data from each of the five contributing studies, allowing us to control for the same set of potential confounders, and standardized categories of alcohol exposure, allowing for more consistent and robust risk estimates. In addition, the large sample size of the consortial approach increased the statistical power to detect associations and interactions.
Studies of Barrett's esophagus help establish where risk factors act in the pathway to esophageal adenocarcinoma, either in the development of Barrett's esophagus or progression from Barrett's esophagus to cancer. A previous pooled analysis of 11 epidemiological studies of esophageal adenocarcinoma in BEACON found suggestive evidence for an inverse association between alcohol and the risk of cancer. However, the summary risk estimates were not statistically significant (expect for those consuming 0.5 to <1.0 drinks/day) and there was no dose–response relationship (Ptrend=0.21). The results of our study of Barrett's esophagus, together with null associations reported for alcohol and the risk of progression from Barrett's esophagus to esophageal adenocarcinoma, provides strong evidence that alcohol consumption is not a risk factor for developing Barrett's esophagus or progressing from Barrett's esophagus to esophageal adenocarcinoma.
We observed some evidence for an inverse relationship with moderate levels of alcohol consumption. It is possible, however, that this may be due, at least in part, to reverse causation. If people with reflux symptoms tend to avoid drinking alcohol, for example, the apparent protective effect may simply be the result of alcohol avoidance among symptomatic cases. Although the associations between alcohol and Barrett's esophagus were not modified by a history of GERD symptoms, we had only self-reported GERD symptoms and the associations were attenuated and not statistically significant when cases were compared with GERD controls. Conversely, one of the component studies found that heavy alcohol consumption at the age of 21 years (well before diagnosis with Barrett's esophagus) was also inversely associated with the risk of Barrett's esophagus, which can be interpreted to argue against reverse causality. There are plausible mechanisms by which alcohol—and wine in particular—may protect against Barrett's esophagus, such as from antioxidant resveratrol, and reduction in insulin resistance or increased levels of lipoproteins. However, as both white wine and red wine have been associated with a lower risk of Barrett's esophagus, resveratrol is unlikely to explain any inverse association.
This pooled analysis has several important strengths, including its large size and inclusion of multiple largely population-based studies. Furthermore, we defined and constructed each alcohol variable in the same way for each study and adjusted our analyses by a standard set of variables known to be associated with Barrett's esophagus. We found no evidence of between-study heterogeneity or evidence that the associations with alcohol were modified by BMI, GERD symptoms, or cigarette smoking.
There are several limitations to this pooled analysis. Most studies ascertained average adult daily consumption, although some studies collected recent consumption and this may have increased the possibility of the reference group of nondrinkers including former drinkers. However, although this would somewhat attenuate the observed associations, it would not explain the inverse association with alcohol. It is possible that our results may be affected by recall and selection bias due to case–control design. However, the possibility of recall bias was minimized, as most studies recruited incident cases soon after diagnosis and subjects in some of the studies were blinded regarding the topic of the study. Although the FINBAR study included both incident and prevalent cases, the associations observed in FINBAR were similar to other studies that used only incident diagnoses. Although our study is the largest to date, we were still unable to examine the association in non-Caucasians, and case numbers were still small in some subgroups of the stratified analyses. Finally, we did not adjust our analyses for diet. However, when two of the component studies adjusted for diet, it did not attenuate the associations with alcohol.
In contrast to esophageal squamous cell carcinoma, where alcohol is a strong risk factor, alcohol consumption is not a risk factor for Barrett's esophagus or esophageal adenocarcinoma. Our findings indicate that alcohol cessation is unlikely to reduce the risk of Barrett's esophagus or esophageal adenocarcinoma. Capturing patients' alcohol histories is therefore unlikely to help improve clinical risk stratification for Barrett's esophagus.
Discussion
In this large pooled analysis, alcohol consumption was not a risk factor for Barrett's esophagus. Compared with controls, average daily consumption of alcohol was moderately lower among cases; however, we found no consistent statistically significant association between alcohol consumption and the risk of Barrett's esophagus, and there was no evidence for a dose–response relationship. In beverage-specific analyses adjusted for total alcohol consumption, wine was associated with a moderately reduced risk of Barrett's esophagus. The association between alcohol and Barrett's esophagus was not modified by other factors (including sex, BMI, GERD, and smoking).
Previous studies have reported associations between alcohol and the risk of Barrett's esophagus; however, results have been conflicting. One possible explanation for the conflicting findings may be that individual studies have inadequate power to assess this association and are prone to type II error. Summarizing these results into an overall risk estimate using only published data is difficult given the different exposure categories, confounders, and analyses used in the published manuscripts. By contrast, in this study, we had access to individual participant data from each of the five contributing studies, allowing us to control for the same set of potential confounders, and standardized categories of alcohol exposure, allowing for more consistent and robust risk estimates. In addition, the large sample size of the consortial approach increased the statistical power to detect associations and interactions.
Studies of Barrett's esophagus help establish where risk factors act in the pathway to esophageal adenocarcinoma, either in the development of Barrett's esophagus or progression from Barrett's esophagus to cancer. A previous pooled analysis of 11 epidemiological studies of esophageal adenocarcinoma in BEACON found suggestive evidence for an inverse association between alcohol and the risk of cancer. However, the summary risk estimates were not statistically significant (expect for those consuming 0.5 to <1.0 drinks/day) and there was no dose–response relationship (Ptrend=0.21). The results of our study of Barrett's esophagus, together with null associations reported for alcohol and the risk of progression from Barrett's esophagus to esophageal adenocarcinoma, provides strong evidence that alcohol consumption is not a risk factor for developing Barrett's esophagus or progressing from Barrett's esophagus to esophageal adenocarcinoma.
We observed some evidence for an inverse relationship with moderate levels of alcohol consumption. It is possible, however, that this may be due, at least in part, to reverse causation. If people with reflux symptoms tend to avoid drinking alcohol, for example, the apparent protective effect may simply be the result of alcohol avoidance among symptomatic cases. Although the associations between alcohol and Barrett's esophagus were not modified by a history of GERD symptoms, we had only self-reported GERD symptoms and the associations were attenuated and not statistically significant when cases were compared with GERD controls. Conversely, one of the component studies found that heavy alcohol consumption at the age of 21 years (well before diagnosis with Barrett's esophagus) was also inversely associated with the risk of Barrett's esophagus, which can be interpreted to argue against reverse causality. There are plausible mechanisms by which alcohol—and wine in particular—may protect against Barrett's esophagus, such as from antioxidant resveratrol, and reduction in insulin resistance or increased levels of lipoproteins. However, as both white wine and red wine have been associated with a lower risk of Barrett's esophagus, resveratrol is unlikely to explain any inverse association.
This pooled analysis has several important strengths, including its large size and inclusion of multiple largely population-based studies. Furthermore, we defined and constructed each alcohol variable in the same way for each study and adjusted our analyses by a standard set of variables known to be associated with Barrett's esophagus. We found no evidence of between-study heterogeneity or evidence that the associations with alcohol were modified by BMI, GERD symptoms, or cigarette smoking.
There are several limitations to this pooled analysis. Most studies ascertained average adult daily consumption, although some studies collected recent consumption and this may have increased the possibility of the reference group of nondrinkers including former drinkers. However, although this would somewhat attenuate the observed associations, it would not explain the inverse association with alcohol. It is possible that our results may be affected by recall and selection bias due to case–control design. However, the possibility of recall bias was minimized, as most studies recruited incident cases soon after diagnosis and subjects in some of the studies were blinded regarding the topic of the study. Although the FINBAR study included both incident and prevalent cases, the associations observed in FINBAR were similar to other studies that used only incident diagnoses. Although our study is the largest to date, we were still unable to examine the association in non-Caucasians, and case numbers were still small in some subgroups of the stratified analyses. Finally, we did not adjust our analyses for diet. However, when two of the component studies adjusted for diet, it did not attenuate the associations with alcohol.
In contrast to esophageal squamous cell carcinoma, where alcohol is a strong risk factor, alcohol consumption is not a risk factor for Barrett's esophagus or esophageal adenocarcinoma. Our findings indicate that alcohol cessation is unlikely to reduce the risk of Barrett's esophagus or esophageal adenocarcinoma. Capturing patients' alcohol histories is therefore unlikely to help improve clinical risk stratification for Barrett's esophagus.
Source...