title: Number of parity and the risk of gallbladder cancer: a systematic review and dose-response meta-analysis of observational studies.
abstract: BACKGROUND
  Current epidemiological evidence suggests an association between parity and risk of gallbladder cancer (GBC), but studies have yielded inconsistent conclusions.
  
  
  OBJECTIVE
  The purpose of this meta-analysis is to systematically analyze the effect of the number of parity on GBC risk.
  
  
  METHODS
  We searched Web of Science, EMBASE, PubMed, China Biological Medicine Database from inception to the end of April 2015. Studies investigating parity and risk of GBC were included. A systematic review and a dose-response meta-analysis were performed to investigate the association between parity and GBC risk using odds ratios (OR) and 95 % confidence intervals (CI).
  
  
  RESULTS
  Thirteen case-control studies were eligible for inclusion in this meta-analysis, including a total of 2,164 cases and 11,340 controls. A significant association was identified for the ever parity vs. nulliparous at 1.39 (95 % CI 1.15-1.68; Power = 0.73; I (2) =0.0 %; P = 0.90). Similarly, the summary estimate for high vs. low parity number was 1.86 (95 % CI 1.51-2.30; Power = 0.26; I (2) = 66.0 % P < 0.01). For the dose-response relationship, a non-linear association between the parity number and GBC risk was not observed (P non-linearity = 0.578), but a clear linear relationship was detected. The combined odds ratio of GBC for an increase in parity of one live birth was 1.12 (95 % CI 1.09-1.21; Power = 0.99; I (2) = 39.9 %; P = 0.139). Subgroup and sensitivity analyses showed similar associations. No publication bias was found in all results. Significant heterogeneity between subgroups was detected by meta-regression analyses.
  
  
  CONCLUSIONS
  In females, higher parity may be associated with an increased risk of gallbladder cancer. In the future, high-quality cohort studies with larger sample sizes and randomized controlled trials are needed to fully scrutinize this association.
authors.affiliation: General Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, 98 Fenghuangbei Road, Zunyi, 563000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Center of Evidence Based and Transformation Medicine of Wuhan University, Wuhan, 430071, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Science and Education, First People's Hospital of Changde City, Changde, 415003, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: JianGuo
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Immunity, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: JuanJuan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Public Health, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, 563099, China.
authors.forename: ZhuangLi
authors.initials: Z
authors.lastname: Si
authors.affiliation: College of Medicine and Nursing of HuBei Medical University, HuBei Medical University, Shiyan, 442200, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shen
authors.affiliation: General Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, 98 Fenghuangbei Road, Zunyi, 563000, China. fengchunlin_zy@163.com.
authors.forename: ChunLin
authors.initials: C
authors.lastname: Feng
mesh_terms: D005260:Female; D005706:Gallbladder Neoplasms / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D064887:Observational Studies as Topic; D010298:Parity; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors
keywords: Dose–response meta-analysis; Gallbladder cancer; Parity; Risk factor; Systematic review