The large size of the pooled database enabled more precise estimates of association than previous studies, particularly in stratified analyses, spline TSA HDAC clinical trial models, and assessment of interaction. Second, although pooling and harmonization of data is a substantial undertaking and requires expertise, time, and resources, individual patient data allows for many benefits over meta-analysis of published estimates, including building consistent models across studies, studying novel questions including interaction, and using novel methods of analysis such as splines. Third, the availability of 2 control groups
for comparison, that is, population-based and GERD, allows us to postulate where risk factors might be active in the pathogenesis of Barrett’s esophagus. This is important because it is feasible that a significant proportion of the population-based control group might unknowingly have Barrett’s esophagus,63 although such misclassification would bias results toward the null. Limitations of this analysis include the moderate-to-high levels of heterogeneity for some analyses. Although constituents of tobacco smoke have
changed over time,64 the studies included in this analysis Trametinib molecular weight recruited incident cases and controls during a similar period (1997–2006). Regardless, constituents of tobacco smoke are likely to have differed geographically as is population susceptibility to genotoxic exposures. The unexplained pentoxifylline heterogeneity does warrant a cautious interpretation of summary estimates, although associations were largely consistent in a majority of studies included, and similar summary estimates with low heterogeneity were estimated when the study that was the source of the most heterogeneity was omitted from analysis. Another limitation is the possibility of recall bias, given the case-control design of the included studies, although the intensity and duration of smoking are usually recalled relatively reliably.65 Lastly, we did not adjust for dietary
variables in this analysis; although previous studies suggest that diet has minimal effects on relationships between smoking and Barrett’s esophagus, there remains the possibility of residual confounding through diet and other exposures. In conclusion, cigarette smoking is a risk factor for Barrett’s esophagus, with adjusted ORs for multiple measures of association in the 1.5 to 2 range. The association appears to strengthen with increased exposure to cigarette smoking until approximately 20 pack-years, where it begins to plateau. If smoking is a causative agent of Barrett’s esophagus, it is an attractive modifiable risk factor, especially in high-risk groups such as elderly, obese males with GERD symptoms.