Genetic variation in the HLA-G 3'UTR 14-bp insertion/deletion and the associated cancer risk: evidence from 25 case-control studies

Abstract

Human leucocyte antigen-G (HLA-G) plays an important role in the progression of human cancers. A growing number of published studies have investigated the correlation between the HLA-G 3' untranslated region (3'UTR) 14-bp insertion/deletion (Ins/Del) polymorphism and the associated cancer risk in different populations. However, results from previous studies are inconclusive and inconsistent for the different type of cancers. Therefore, we undertook a meta-analysis to assess the effects of the HLA-G 14-bp Ins/Del polymorphism on cancer risk. A systematic literature search was conducted in PubMed, Web of Science, CNKI, VIP, and Wanfang databases to obtain relevant studies up to 28 January 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used. Twenty-five published case-control studies comprising 4981 cases and 6391 controls were included in the current meta-analysis. The results of the overall analysis revealed that the HLA-G 14-bp Ins/Ins genotype and Ins allele were associated with the total cancer risk in the homozygote comparison model (Ins/Ins vs. Del/Del: OR = 0.80, CI = 0.64-1.00; P=0.049) and the allelic comparison model (Ins vs. Del: OR = 0.89, CI = 0.81-0.99; P=0.035), with a protective role. Further subgroup analyses indicated that the HLA-G 14-bp Ins/Del polymorphism was associated with the risk of breast cancer and oesophageal cancer (EC), and significant risk of cancer was also observed in Mixed populations and population-based (PB). The results of our meta-analysis show that the HLA-G 14-bp Ins/Del polymorphism plays an important role in cancer risk, particularly in breast cancer and esophageal cancer in Mixed populations. Additional case-control studies with different types of cancer spanning different ethnicities are needed to extend the present findings.

Keywords: Cancer; Human leukocyte antigen-G; Meta-analysis; Polymorphism.

Figure 1. The flow diagram of the included and excluded studies

Figure 2. Forest plots of the HLA-G 14-bp Ins/Del polymorphism and cancer risk (homozygote comparisons: Ins/Ins vs. Del/Del)

Figure 3. Forest plots of the HLA-G 14–bp Ins/Del polymorphism and cancer risk (allelic comparisons: Ins vs. Del)

Figure 4. Sensitivity analysis of the HLA-G 14-bp Ins/Del polymorphism and cancer risk (homozygote comparisons: Ins/Ins vs. Del/Del)

Figure 5. Funnel plot assessing evidence of publication bias (homozygote comparisons: Ins/Ins vs. Del/Del)