title: The non-linear threshold association between aspirin use and esophageal adenocarcinoma: results of a dose-response meta-analysis.
abstract: BACKGROUND
  The role of aspirin use in chemoprevention of esophageal adenocarcinoma (EAC) is still unclear. Previous meta-analyses have reported a beneficial effect of aspirin use, whereas it remains still under debate whether there are non-linear frequency-risk and duration-risk relations, such as a "threshold" effect.
  
  
  METHODS
  Nine observational studies reporting the association between aspirin use and EAC risk were selected through a combined search with the PUBMED and EMBASE electronic databases of articles published before June 2013. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models, and the cubic spline regression models were performed for the study of frequency-risk and duration-risk relations.
  
  
  RESULTS
  A monotonically decreasing relation was observed only for ≤ 4.5 times per week (OR=0.75, 95%CI 0.64-0.88, for twice per week; OR=0.59, 95%CI 0.45-0.78, for 4.5 times per week) and ≤ 6 years (OR=0.82, 95%CI 0.76-0.91, for 1 year; OR=0.53, 95%CI 0.37-0.75, for 3 years) of aspirin use using the non-users as the reference. Once the frequency is more than 4.5 times/week or the duration is longer than 6 years, no further benefit was observed.
  
  
  CONCLUSIONS
  Our findings suggest that there may be non-linear threshold relations of frequency and duration of aspirin use with the risk of EAC. Further data from randomized clinical trials are required.
authors.affiliation: School of Public Health, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China; School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiaohua
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhenjiang
authors.forename: Liu
authors.initials: L
authors.lastname: Weidong
authors.forename: Xun
authors.initials: X
authors.lastname: Pengcheng
authors.forename: Chen
authors.initials: C
authors.lastname: Sidong
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D017711:Nonlinear Dynamics; D064887:Observational Studies as Topic / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin
keywords: aspirin; epidemiology; esophageal cancer; nonsteroidal anti-inflammatory drugs; pharmacoepidemiology