In Response: As Camargo et al. have pointed out, two recently published meta-analyses in Cancer Epidemiology, Biomarkers, and Prevention (1, 2) with somewhat different choices of studies and analytic approach found slightly different summary estimates for the association of interleukin-1B-511 T polymorphisms with gastric cancer in Caucasian populations. Both studies, however, found substantial heterogeneity in overall and subgroup results, including among studies in Caucasian populations.
We believe that, in the presence of substantial heterogeneity, summary estimates are useful but should not be the main focus of interpreting meta-analysis results. Heterogeneity may reflect complex combinations of factors that lead to a common outcome of cancer. The effect of interleukin-1B polymorphisms on functional transcription varies due to epistatic interaction (3). More broadly, the multiple components of both genetic and environmental factors may have different interactions in different populations, such that an individual “cause” in one group may be irrelevant in another. As a hypothetical scenario, a proinflammatory diathesis might minimize Helicobacter pylori replication given a particular age of acquisition and sufficient intake of fresh foods but exacerbate severity of consequent gastritis in the presence of a particular blood group and a diet high in salt.
Because the sources of heterogeneity are unknown, the pathophysiologic effect of interleukin-1B polymorphisms on H. pylori infection, hypochlorhydric response, and other factors related to gastric cancer should be explored. The relationship between interleukin-1B polymorphisms and precancerous lesions may also be informative: several studies have found relatively strong associations in both Caucasians (4) and Asians (5-7). Conceivably, the effect of interleukin-1B polymorphisms may be greater early in the pathogenesis of gastric cancer but attenuate in subsequent stages that have other governing factors. This hypothesis could be formally evaluated in a systematic review of the literature.
Volume 16, Issue 3
