HLA-G +3142 C>G polymorphism and cancer risk: Evidence from a meta-analysis and trial sequential analysis

Human leukocyte antigen-G (HLA-G) plays an important role in the development of human cancers. Several published studies have investigated the relationship between the HLA-G +3142 C>G (rs1063320) polymorphism and cancer susceptibility in different populations. However, the results have yet to reach a consensus in different types of cancers. Therefore, we performed a meta-analysis to evaluate the effect of the HLA-G +3142 C>G polymorphism on cancer risk.

A systematic literature search was performed in PubMed, Web of Science, CNKI, VIP, and Wanfang databases to acquire eligible studies up to February 20, 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the correlation between the HLA-G +3142 C>G polymorphism and cancer risk in a fixed-effects or random-effects model. Publication bias assessments, sensitivity analysis and stratified analyses were performed. To reduce the risk of type I error and assess whether the present evidence of the results was adequate and conclusive, trial sequential analysis (TSA) was also performed.

Eight case-control studies comprising 1546 cases and 1595 controls were included in the present meta-analysis. The results revealed that the HLA-G +3142 C>G mutation significantly decreased the total cancer risk in recessive comparison model and allelic comparison model. Further stratified analyses showed that the HLA-G +3142 C>G mutation significantly decreases the risk of cancer in Asian populations. No similar relationship was found in other subgroups. No publication bias was identified in our present study. Omitting a single study at a time had no significant impact on the pooled OR of the sensitivity analysis assessing the association between the HLA-G +3142 C>G polymorphism and cancer risk, which demonstrates the stability of the current meta-analysis. TSA also identified our current findings.

The results of our meta-analysis show that the HLA-G +3142 C>G polymorphism plays a protect role in the occurrence of human cancers, particularly in Asian populations. More case-control studies with different types of cancer in various ethnicities are needed to verify the findings.