title: Random-effects meta-regression models for studying nonlinear dose-response relationship, with an application to alcohol and esophageal squamous cell carcinoma.
abstract: A fundamental challenge in meta-analyses of published epidemiological dose-response data is the estimate of the function describing how the risk of disease varies across different levels of a given exposure. Issues in trend estimate include within studies variability, between studies heterogeneity, and nonlinear trend components. We present a method, based on a two-step process, that addresses simultaneously these issues. First, two-term fractional polynomial models are fitted within each study included in the meta-analysis, taking into account the correlation between the reported estimates for different exposure levels. Second, the pooled dose-response relationship is estimated considering the between studies heterogeneity, using a bivariate random-effects model. This method is illustrated by a meta-analysis aimed to estimate the shape of the dose-response curve between alcohol consumption and esophageal squamous cell carcinoma (SCC). Overall, 14 case-control studies and one cohort study, including 3000 cases of esophageal SCC, were included. The meta-analysis provided evidence that ethanol intake was related to esophageal SCC risk in a nonlinear fashion. High levels of alcohol consumption resulted in a substantial risk of esophageal SCC as compared to nondrinkers. However, a statistically significant excess risk for moderate and intermediate doses of alcohol was also observed, with no evidence of a threshold effect.
authors.affiliation: Department of Statistics, Università degli Studi di Milano-Bicocca, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Rota
authors.forename: Rino
authors.initials: R
authors.lastname: Bellocco
authors.forename: Lorenza
authors.initials: L
authors.lastname: Scotti
authors.forename: Irene
authors.initials: I
authors.lastname: Tramacere
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D006801:Humans; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D012044:Regression Analysis; D012306:Risk