title: Paracetamol use and risk of ovarian cancer: a meta-analysis.
abstract: OBJECTIVE
  Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature.
  
  
  METHODS
  A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models.
  
  
  RESULTS
  Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR=0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR=0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR=0.70, 95% CI 0.51, 0.95).
  
  
  CONCLUSIONS
  Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Athens, Athens, Greece. sbonovas@med.uoa.gr
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.forename: Kalitsa
authors.initials: K
authors.lastname: Filioussi
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Sitaras
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D000082:Acetaminophen