Pancreatitis-Associated Genes and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis

Pancreas. 2018 Oct;47(9):1078-1086. doi: 10.1097/MPA.0000000000001145.

Abstract

Objective: The aim of this study was to evaluate the connection between pancreatic cancer (PC) and genetic variants associated with chronic pancreatitis via systematic review and meta-analysis.

Methods: The data search was performed in 3 major databases (PubMed, Embase, and Cochrane Library). The selected studies have looked into the presence of the pancreatitis-associated genes in patients with PC and in control subjects, the outcome being the frequency of the mutations in the 2 groups. For the binary outcomes, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated.

Results: Ten articles proved to be eligible for the qualitative synthesis, and 8 articles were suitable for statistical analysis. Six case-control studies, comprising 929 PC cases and 1890 control subjects for serine protease inhibitor Kazal type 1 (SPINK1) mutations, and 5 case-control studies, comprising 1674 PC cases and 19,036 control subjects for CFTR mutations, were enrolled in our analysis. SPINK1 mutations showed no association with PC (OR, 1.52; 95% CI, 0.67-3.45; P = 0.315), whereas mutations in CFTR modestly increased the risk of PC (OR, 1.41; 95% CI, 1.07-1.84; P = 0.013).

Conclusion: Our meta-analysis showed that mutations in CFTR modestly increase the risk of PC, whereas no association was found between SPINK1 and PC.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mutation*
  • Odds Ratio
  • Pancreatic Neoplasms / genetics*
  • Pancreatitis, Chronic / genetics*
  • Risk Factors
  • Trypsin Inhibitor, Kazal Pancreatic / genetics

Substances

  • CFTR protein, human
  • SPINK1 protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic