Single Nucleotide Polymorphisms and Post-operative Complications Following Major Gastrointestinal Surgery: a Systematic Review and Meta-analysis

Abstract

Background: The human genome is an under-researched area of pre-operative risk stratification. Studies of genetic polymorphisms and their associations with acute post-operative complications in gastrointestinal surgery have reported statistically significant results, but have varied in methodology, genetic variations studied, and conclusions reached. To provide clarity, we conducted a systematic review and meta-analysis of single nucleotide polymorphisms and their association with post-operative complications after major gastrointestinal surgery.

Methods: We performed a literature search using Ovid MEDLINE and Web of Science databases. Studies were included if they investigated genetic polymorphisms and their associations with post-operative complications after major gastrointestinal surgery. We extracted clinical and genetic data from each paper and assessed for quality against the STrengthening the REporting of Genetic Association Studies (STREGA) guidelines. Odds ratios were presented, with 95% confidence intervals, to assess strengths of association. We conducted a meta-analysis on TNF-α-308, which had been assessed in three papers.

Results: Our search returned 68 papers, of which 5 were included after screening and full-text review. Twenty-two different single nucleotide polymorphisms (SNPs) were investigated in these studies. We found that all papers were genetic association studies, and had selected SNPs related to inflammation. The outcome investigated was most commonly post-operative infection, but also anastomotic leak and other non-infectious complications. Statistically significant associations were found for TNF-α-308, IL-10-819, PTGS2-765 and IFN-γ-874. There was significant variability in study quality and methodology. We conducted a meta-analysis on associations between the TNF-α-308 polymorphism and post-operative infection and report an OR of 1.18 (CI 0.27-5.21).

Conclusions: We found biologically plausible associations between SNPs involved in inflammation and post-operative infection, but the available data were too limited and of insufficient quality to reach definitive conclusions. Further work is needed, including genome-wide association studies (GWAS).

Keywords: Gastrointestinal surgery; Genetics; Post-operative complications.

Fig. 1

Flow chart of study identification, exclusion and inclusion. Adapted from the PRISMA statement

Fig. 2

Forest plot demonstrating TNF-α-308 and risk of infection, using an allele contrast model (A vs G)