Open AccessThe relationship of 3′UTR HLA‐G14‐bp insertion/deletion and +3142 C/G polymorphisms and soluble HLA‐G expression with gynecological cancers: An updated meta‐analysis
Author(s) -
Tizaoui Kalthoum,
Jalouli Maroua,
Boujelbene Nadia,
Harrath Abdel Halim,
Ouzari HaddaImene,
Rizzo Roberta,
Zidi Inès
Publication year - 2022
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.645
Subject(s) - hla g , odds ratio , genotype , allele , human leukocyte antigen , medicine , meta analysis , cervical cancer , confidence interval , single nucleotide polymorphism , gastroenterology , oncology , biology , immunology , cancer , genetics , antigen , gene
Objectives Human leukocyte antigen‐G (HLA‐G) is implicated in several cancers and is considered to be an immune checkpoint regulator. We determined the association between polymorphisms in the 3′ untranslated region of HLA‐G and soluble HLA‐G (sHLA‐G) expression with gynecological cancers (GCs). Methods A meta‐analysis was conducted to examine the association between HLA‐G14‐bp insertion ( I )/ deletion ( D ) and +3142C/G polymorphism in GC and to evaluate sHLA‐G expression Results We revealed a significant association between the +3142C/G polymorphism and invasive cervical cancer (ICC) based on the allelic model G versus C (odds ratio [OR] = 0.738, 95% confidence interval [CI] = 0.563–0.966, p = 0.027), dominant GG+GC versus CC (OR = 0.584, 95% CI = 0.395–0.862, p = 0.007), and codominant GG versus CC (OR = 0.527, 95% CI = 0.312–0.891, p = 0.017) models, suggesting that the G allele and GG genotype are protective against ICC. In gynecological precancerous patients with human papillomavirus (HPV) infection, we found that the 14‐bp I/D under the codominant DD versus DI model (OR = 0.492, 95% CI = 0.241–1.004, p = 0.051) was of borderline significance. Soluble HLA‐G levels were significantly higher in patients compared with healthy controls (standardized mean differences [SMD] = 1.434, 95% CI = 0.442–2.526, p = 0.005). Stratification by cancer type revealed that the sHLA‐G levels were significantly increased in cervical cancer (SMD = 4.889, 95% CI = 0.468–9.310, p = 0.030) and in subjects of Asian ethnicity (SMD = 4.889, 95% CI = 0.467–9.309, p = 0.030). Conclusions HLA‐G14‐bp I/D and +3142 C/G polymorphisms are associated with GC and HPV‐associated cervical cancer. In addition, we found significantly increased sHLA‐G levels in cancer patients. These results provide a basis for further studies in diagnostics and immunotherapy of GC.