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14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

  • Haghi, Mehdi (Department of Genetics, Faculty of Natural Sciences, University of Tabriz) ;
  • Feizi, Mohammad Ali Hosseinpour (Department of Genetics, Faculty of Natural Sciences, University of Tabriz) ;
  • Sadeghizadeh, Majid (Department of Genetics, Faculty of Biological Sciences, Tarbiat Modarres University) ;
  • Lotfi, Abbas Sahebghadam (Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modarres University)
  • Published : 2015.09.02

Abstract

Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (${\chi}^2=4.16$, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

References

  1. Aflakseir A, Abbasi P (2012). Health beliefs as predictors of breast cancer screening behavior in a group of female employees in Shiraz. Iranian J Cancer Prev, 5, 124-9.
  2. Amiot L, Ferrone S, Grosse-Wilde H, Seliger B (2011). Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention? Cell Mol Life Sci, 68, 417-31. https://doi.org/10.1007/s00018-010-0583-4
  3. Burnet FM (1957). Cancer- a biological approach: I. the processes of control. II. the significance of somatic mutation. Brit Med Jour, 1, 779-786. https://doi.org/10.1136/bmj.1.5022.779
  4. Castelli EC, Mendes-Junior CT, Deghaide NH, et al (2010). The genetic structure of 3'untranslated region of the HLA-G gene: polymorphisms and haplotypes. Genes Immun, 112, 134-41.
  5. Castelli EC, Ramalho J, Porto I, Lima T, et al (2014). Insights into HLA-G genetics provided by worldwide haplotype diversity. Frontiers in Immunology, 5, 476.
  6. Curigliano G, Criscitiello C, Lucia Gelao L, Goldhirsch A (2013). Molecular pathways: Human Leukocyte Antigen G (HLA-G). Clin Cancer Res, 19, 5564-71 https://doi.org/10.1158/1078-0432.CCR-12-3697
  7. Eivazi-Ziaei J, Dastgiri S, Asvadi Kermani I, et al (2011). Age pattern of the occurrence of breast cancer in the northwest of Iran. Indian J Cancer, 48, 406-9 https://doi.org/10.4103/0019-509X.92256
  8. Elliott RL, Jiang XP, Phillips JT, Barnett BG, Head JF (2011). Human leukocyte antigen G expression in breast cancer: role in immunosuppression. Cancer Biother Radiopharm, 26, 153-7 https://doi.org/10.1089/cbr.2010.0924
  9. Ellis SA, Sargent IL, Redman CW, McMichael AJ (1986). Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology, 59, 595-601.
  10. Enghelabifar M, Allafan S, Khayatzadeh J (2014). Association of the maternal 14-bp insertion/deletion polymorphism in the histocompatibility leukocyte antigen G gene with recurrent implantation failure. Iran J Reprod Med, 12, 641-6.
  11. Eskandari-Nasab E, Hashemi M, Hasani SS, et al (2013). Association between HLA-G 3'UTR 14-bp ins/del polymorphism and susceptibility to breast cancer. Cancer Biomarkers, 13, 253-9.
  12. Gonzalez A, Rebmann V, LeMaoult J, et al (2012). The immunosuppressive molecule HLA-G and its clinical implications. Crit Rev Clin Lab Sci, 49, 63-84. https://doi.org/10.3109/10408363.2012.677947
  13. Harrison GA, Humphrey KE, Jakobsen IB, Cooper DW (1993). A 14 bp deletion polymorphism in the HLA-G gene. Hum Mol Genet, 2, 2200.
  14. Hviid TV, Larsen LG, Hoegh AM, Bzorek M (2004). HLA-G expression in placenta in relation to HLA-G genotype and polymorphisms. Am J Reprod Immunol, 52, 212-7. https://doi.org/10.1111/j.1600-0897.2004.00208.x
  15. Jeong S, Seho Park S, Park B, et al (2014). Human Leukocyte Antigen-G (HLA-G) polymorphism and expression in breast cancer patients. PlosOne, 9, 98284 https://doi.org/10.1371/journal.pone.0098284
  16. Kovats S, Main EK, Librach C, et al (1990). Class I antigen, HLA-G, expressed in human trophoblasts. Science, 248, 220-3. https://doi.org/10.1126/science.2326636
  17. Kuroshli Z, Gourabi H, Bazrgar M, et al (2014). HLA-G allele and haplotype frequencies in a healthy population of Iran. Iran J Allergy Asthma Immunol, 13, 207-13.
  18. Larsen MH, Hviid TV (2009). Human leukocyte antigen-G polymorphism in relation to expression, function, and disease. Hum Immunol, 70, 1026-34. https://doi.org/10.1016/j.humimm.2009.07.015
  19. Manaster I, Goldman-Wohl D, Greenfield C (2012). MiRNAmediated control of HLA-G expression and function. PlosOne ,7, 33395. https://doi.org/10.1371/journal.pone.0033395
  20. Martelli G, Pancotto JA, Muniz YC, et al (2013). Polymorphic sites at the 3’ untranslated region of the HLA-G gene are associated with differential hla-g soluble levels in the Brazilian and French population. PlosOne, 8, 71742 https://doi.org/10.1371/journal.pone.0071742
  21. Moon A, Kim S, Ghung J, et al (2011). 14-bp Insertion/Deletion polymorphism of the HLA-G Gene in Osteosarcoma Patients. The Korean Journal of Pathology, 45, 485-490. https://doi.org/10.4132/KoreanJPathol.2011.45.5.485
  22. Pouladi N, Kouhsari SM, Feizi MH, et al (2014). Lack of association of intron 3 16 bp polymorphism of TP53 with breast cancer among Iranian-Azeri patients. Asian Pac J Cancer Prev, 15, 2631-4. https://doi.org/10.7314/APJCP.2014.15.6.2631
  23. Rousseau P, Le Discorde M, Mouillot G, et al (2003).The 14 bp deletion-insertion polymorphism in the 3' UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol, 64, 1005-10. https://doi.org/10.1016/j.humimm.2003.08.347
  24. Saadatian Z, Gharesouran J, Ghojazadeh M, et al (2014). Association of rs1219648 in FGFR2 and rs1042522 in TP53 with premenopausal breast cancer in an Iranian Azeri population. Asian Pac J Cancer Prev, 15, 7955-8. https://doi.org/10.7314/APJCP.2014.15.18.7955
  25. Sedaie A, Pouladi N, Hosseinpourfeizi MA, et al (2014). Singlestrand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population. Med Oncol, 31, 168. https://doi.org/10.1007/s12032-014-0168-4
  26. Somi MH, Mousavi SM, Rezaeifar P, Naghashi SH (2009) Cancer incidence among the Elderly population in the northwest of Iran: A population based study. Iranian J Cancer Prev, 2, 117-126.
  27. Taghavi A, Fazeli Z, Vahedi M, et al (2012). Increased trend of breast cancer mortality in Iran. Asian Pac J Cancer Prev, 13, 367-70. https://doi.org/10.7314/APJCP.2012.13.1.367
  28. Tripathi P, agrawal S (2006). Non-classical HLA-G antigen and its role in the cancer progression Cancer Invest, 24,178-86. https://doi.org/10.1080/07357900500524579
  29. Tuncel T, Karagoz B, Haholu A, et al (2013). Immunoregulatory function of HLA-G in gastric cancer. Asian Pac J Cancer Prev, 14, 7681-4. https://doi.org/10.7314/APJCP.2013.14.12.7681
  30. Veit TD, Chies JA (2009). Tolerance versus immune response - microRNAs as important elements in the regulation of the HLA-G gene expression. Transpl Immunol, 20, 229-31. https://doi.org/10.1016/j.trim.2008.11.001
  31. Wang X1, Jiang W, Zhang D (2013) Association of 14-bp insertion/deletion polymorphism of HLA-G gene with unexplained recurrent spontaneous abortion: a meta-analysis. Tissue Antigens, 81, 108-15. https://doi.org/10.1111/tan.12056
  32. Yz G, Q G, MH L, et al (2014). Association between human leukocyte antigen-G 14-bp insertion/deletion polymorphism and cancer risk: a meta-analysis and systematic review. Hum Immunol, 75, 827-32 https://doi.org/10.1016/j.humimm.2014.06.004