title: Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease.
abstract: BACKGROUND
  Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory.
  
  
  OBJECTIVE
  To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease.
  
  
  METHODS
  We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs).
  
  
  RESULTS
  One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers.
  
  
  CONCLUSIONS
  This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease.
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
authors.forename: W-Q
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Sun
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
authors.forename: R-T
authors.initials: RT
authors.lastname: Zhu
authors.affiliation: Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Wang
mesh_terms: D016022:Case-Control Studies; D003069:Coffee; D004305:Dose-Response Relationship, Drug; D005260:Female; D042882:Gallstones / Q000517:prevention & control*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012306:Risk; D012737:Sex Factors
chemical_list: D003069:Coffee