The 14-bp insertion/deletion as a promising gene polymorphism to understand cancer risk: Evidence from a systematic review and comprehensive meta-analysis.

Autor:	Tizaoui K; Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunisia., Ayadi MA; Department of Surgical Oncology, Salah Azaiz Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Zemni I; Department of Surgical Oncology, Salah Azaiz Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Harrath AH; King Saud University, College of Science, Department of Zoology, Riyadh, Saudi Arabia., Rizzo R; Department of Environmental and Prevention Sciences, University of Ferrara, Ferrara, Italy., Boujelbene N; Department of Pathology, Salah Azaiz Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Zidi I; Laboratory of Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Oct 23; Vol. 10 (22), pp. e39740. Date of Electronic Publication: 2024 Oct 23 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e39740
Abstrakt:	Background: HLA-G is associated with cancer cell escape. The 3'UTR polymorphism is involved in the regulation of membrane-bound HLA-G and soluble HLA-G proteins. The aim of our study was to assess the association of the HLA-G 14-bp insertion (I)/deletion (D) polymorphism with cancer susceptibility and its interaction with clinicopathological features and environmental factors. Methods: A meta-analysis was performed to investigate the association between the HLA-G 14-bp I/D polymorphism and different types of cancers according to the Prisma guidelines. Results: Thirty-nine publications that studied the 14-bp I/D polymorphism in cancers met our inclusion criteria. The findings of the meta-analysis showed a significant association between the 14-bp I/D polymorphism and cancer risk under the allelic contrast model D vs. I (OR = 1,112, 95 % CI = 1,009-1,227; P = 0,033) suggesting that the D allele was a risk factor for cancer susceptibility. Stratification by cancer type demonstrated a significant association of the 14-bp I/D polymorphism with breast cancer under the D vs. I contrast allele model (OR = 1,267, 95 % CI = 1,028-1,563; P  = 0,027). No significant association was found for digestive, cervical, haematological and thyroid cancers. A comparison of groups stratified by ethnicity showed a significant association for Caucasians under the D vs. I model (OR = 1,147, 95 % CI = 1,002-1,313; P  = 0,047); and for mixed ethnicities under the DD + DI vs. II (OR = 1,388, 95 % CI = 1,083-1,780; P  = 0,010) and DI vs. II (OR = 1,402, 95 % CI = 1,077-1,824; P  = 0,012) models. A comparison of cancer risks associated with the 14-bp I/D polymorphism according to geographic location revealed significant risks for the D allele and DD genotype in North Africa, the Middle East and South America. However, no significant susceptibility to cancer associated with the 14-bp I/D polymorphism was shown for Europe and North Asia. The findings of a meta-analysis of subgroups by disease stage showed a significant association in both early and advanced stages, with the 14-bp deletion variant being a risk factor. Similarly, a significant cancer risk was shown for the 14-bp deletion variant in both low- and high-grade cancers. Finally, the risk associated with the 14-bp I/D polymorphism was higher in cancers with concomitant viral infection with human papillomavirus (HPV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Conclusion: The findings of the overall meta-analysis showed a significant association between the HLA-G 14-bp I/D polymorphism and cancer susceptibility. The findings stratified analysis and subgroup comparisons showed that the 14-bp I/D deletion variant was associated with an increased risk of breast cancer. The HLA-G 14-bp I/D polymorphism may interact with individual and clinicopathological factors to alter cancer risk. These promising findings for cancer risk provide the basis for further studies that explore 14bp I/D polymorphism in cancer screening and immunotherapeutic approach. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ines Zidi is currently serving as an Associate Editor for Heliyon Immunology. Although she was not involved in the review of this specific manuscript, she is disclosing this position to ensure transparency and uphold the integrity of the review process for this submission. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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