Association of HLA-G Polymorphism at rs66554220 14-bp Insertion/Deletion Variant with HPV-Related Cervical Cancer: A Cross-Sectional Study
HLA-G Polymorphism and HPV-Related Cervical Cancer
DOI:
https://doi.org/10.61919/jhrr.v4i3.1611Keywords:
HLA-G polymorphism, HPV, cervical cancer, 14-bp deletion, immune response, genetic susceptibility, PCR, molecular analysis, gynecologyAbstract
Background: Cervical cancer is a major cause of cancer-related morbidity and mortality in women globally, predominantly caused by persistent infection with high-risk human papillomavirus (HPV) types. Genetic factors, including HLA-G polymorphisms, may contribute to HPV-related cervical cancer susceptibility.
Objective: To evaluate the association of HLA-G polymorphism at rs66554220 with HPV-related cervical cancer in women presenting to a gynecology OPD.
Methods: A cross-sectional study was conducted at Ziauddin Hospital from January 2023 to May 2024. Cervical smear samples were obtained from 41 women, and DNA was extracted for genotyping using the QIAamp DNA Mini Kit. HPV detection was performed using PCR with L1-specific primers, and HLA-G polymorphism at rs66554220 was analyzed using PCR and Sanger sequencing. Statistical analysis was performed using SPSS version 25, with significance set at p < 0.05.
Results: The 14-bp deletion variant was found in 26.8% of participants, and 19.5% tested positive for HPV. The deletion polymorphism significantly increased HPV-related cervical cancer risk (χ² = 27.1, OR = 12.7, 95% CI: 3.14–51.56, p < 0.001).
Conclusion: The HLA-G polymorphism at rs66554220 is significantly associated with HPV-related cervical cancer, suggesting its potential role in cervical cancer screening.
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References
Clifford GM, Smith JS, Plummer M, Muñoz N, Franceschi S. Human Papillomavirus Types in Invasive Cervical Cancer Worldwide: A Meta-Analysis. British Journal of Cancer. 2003;88(1):63-73.
Jiang Y, Chen S, Jia S, Zhao H. Impact of HLA-G 14-bp Insertion/Deletion Polymorphism on the Risk of Cancer: A Meta-Analysis. Oncotarget. 2016;7(9):8554-8562.
Castelli EC, Mendes-Junior CT, Deghaide NH, et al. HLA-G 14-bp Polymorphism and +3142G>C Variants Are Associated With Differential HLA-G mRNA Levels in High-Risk HPV-Infected Women. BMC Cancer. 2011;11:357.
Rouas-Freiss N, Moreau P, Ferrone S, Carosella ED. HLA-G Proteins in Cancer: Do They Provide Tumor Cells With an Escape Mechanism? Cancer Research. 2005;65(22):10139-10144.
Teixeira AC, Mendes-Junior CT, Souza FF, et al. The Influence of HLA-G 3′UTR Polymorphisms on Cervical Cancer Risk in a Brazilian Population. Tissue Antigens. 2013;82(1):71-76.
Bortolotti D, Gentili V, Rotola A, et al. Impact of HLA-G 14-bp Polymorphism and IL-10 on HPV Infection and Squamous Intraepithelial Lesions. Journal of Immunology Research. 2016;2016:5864950.
Larsen MH, Zinyama R, Kallestrup P, et al. HLA-G Polymorphisms in Relation to HIV Status and Pregnancy Outcome in Zimbabwean Women. PLoS One. 2013;8(6).
Guimarães V, Soares CP, Donadi EA, et al. Influence of HLA-G 14-bp Deletion/Insertion Polymorphism in HPV Infection and in the Development of Cervical Lesions. Human Immunology. 2012;73(10):970-975.
Yoon JA, Cha JH, Kim JE, Lee SK, et al. Association of HLA-G Polymorphisms With Cervical Intraepithelial Neoplasia in Korean Women. Human Immunology. 2007;68(11):1030-1034.
Ferguson R, Ramanakumar AV, Koushik A, et al. HLA-G and HLA-E Variants Are Associated With Risk of Cervical Cancer. Human Immunology. 2012;73(3):293-297.
Silva LM, Galvão BB, Minucci EG, et al. Association Between HLA-G Polymorphisms and HPV Infection in Brazilian Patients With Cervical Lesions. Journal of Clinical Virology. 2013;58(4):652-657.
Dong P, Hanley SJB, Yue J, et al. UHRF1 Promotes Cell Proliferation and Cyclin D1 Gene Transcription by Downregulation of p16INK4a in Cervical Cancer Cells. Oncogenesis. 2014;3(11).
Zhou C, Zhang Y, Cao H, et al. HLA-G 14-bp Insertion/Deletion Polymorphism and Susceptibility to Esophageal Cancer in a Kazakh Population. Cancer Biomarkers. 2016;17(1):59-65.
Huihui X, Chun Y, Lan P, et al. Association of HLA-G Gene 14-bp Deletion/Insertion Polymorphism With the Risk of Cervical Cancer: A Meta-Analysis. Oncotarget. 2018;9(6):6654-6662.
Ferugson R, Ramanakumar AV, Koushik A, et al. HLA-G and HLA-E Variants Are Associated With Risk of Cervical Cancer. Human Immunology. 2012;73(3):293-297.
Eskandari-Nasab E, Moghadampour M, Pourmasoumi H, Shokouhi B. Association of HLA-G 14-bp Insertion/Deletion Polymorphism with Cancer: A Meta-Analysis. Asian Pacific Journal of Cancer Prevention. 2014;15(8):3361-3367.
Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. Chapter 1: HPV in the Etiology of Human Cancer. Vaccine. 2006;24(Suppl 3).
Carosella ED, Rouas-Freiss N, Roux DT, et al. HLA-G Function in Tumor Escape Mechanisms. Cancer Letters. 2011;311(2):180-187.
Rouas-Freiss N, Goncalves RM, Menier C, et al. Direct Evidence to Support the Role of HLA-G in Immune Evasion. Human Immunology. 1997;58(11):752-753.
Schollkopf C, Melbye M, Munksgaard L, et al. Risk of Cervical Cancer in Women With HIV Infection: A Population-Based Cohort Study. Journal of the National Cancer Institute. 2010;102(11):797-804.
Wang SS, Ziegler RG, Yu K, et al. Polymorphisms in Immune and DNA Repair Genes and the Risk of Human Papillomavirus Persistence and Progression to Cervical Cancer. Cancer Research. 2007;67(12):6102-6110.
Rodriguez AC, Schiffman M, Herrero R, et al. Longitudinal Study of Human Papillomavirus Persistence and Cervical Intraepithelial Neoplasia Grade 2/3: Critical Role of Duration of Infection. Journal of the National Cancer Institute. 2010;102(5):315-324.
Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N. HLA-G: From Biology to Clinical Benefits. Trends in Immunology. 2008;29(3):125-132.
Gadducci A, Barsotti C, Cosio S, et al. Cervical Cancer Prevention: Current Strategies and Unresolved Issues. Gynecologic Oncology. 2011;121(3):601-607.
Schiffman M, Wentzensen N, Wacholder S, et al. Human Papillomavirus Testing in the Prevention of Cervical Cancer. Journal of the National Cancer Institute. 2011;103(5):368-383.
Lazarte J, Leguisamo M, Martos M, et al. HLA-G as a Tumor Biomarker. Immunology Letters. 2019;213:1-10.
Yan WH, Lin A, Chen XJ. The Association of HLA-G Polymorphism With Cancer Susceptibility: A Meta-Analysis. International Journal of Cancer. 2010;127(2):494-504.
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