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Lack of any Association of the CTLA-4 +49 G/A Polymorphism with Breast Cancer Risk in a North Indian Population

  • Published : 2014.03.01

Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an important protein involved in the regulation of the immune system. The +49 G/A polymorphism is the only genetic variation in the CTLA-4 gene that causes an amino acid change in the resulting protein. It is therefore the most extensively studied polymorphism among all CTLA-4 genetic variants and contributions to increasing the likelihood of developing cancer are well known in various populations, especially Asians. However, there have hiterto been no data with respect to the effect of this polymorphism on breast cancer susceptibility in our North Indian population. We therefore assayed genomic DNA of 250 breast cancer subjects and an equal number of age-, sex- and ethnicity-matched healthy controls for the CTLA-4 +49 G/A polymorphism but no significant differences in either the gene or allele frequency were found. Thus the CTLA-4 +49 G/A polymorphism may be associated with breast cancer in other Asians, but it appears to have no such effect in North Indians. The study also highlights the importance of conducting genetic association studies in different ethnic populations.

References

  1. Zhang B, Beeghly-Fadiel A, Long J, et al (2011). Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol, 12, 477-88. https://doi.org/10.1016/S1470-2045(11)70076-6
  2. Takiar R, Nadayil D, Nandakumar A (2010). Projections of number of cancer cases in India (2010-2020) by cancer groups. Asian Pac J Cancer Prev, 11, 1045-9.
  3. Sun T, Hu S, Shen H, et al (2009). Genetic polymorphisms in cytotoxic T-lymphocyte antigen 4 and cancer: the dialectical nature of subtle human immune dysregulation. Cancer Res, 69, 6011-4.
  4. Ueda H, Howson JM, Esposito L, et al (2003). Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 423, 506-11 https://doi.org/10.1038/nature01621
  5. Wang L, Li D, Fu Z, et al (2007). Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population. BMC Cancer, 7, 173. https://doi.org/10.1186/1471-2407-7-173
  6. Reiman JM, Kmieciak M, Manjili MH, et al (2007). Tumor immunoediting and immunosculpting pathways to cancer progression. Semin Cancer Biol, 17, 275-87. https://doi.org/10.1016/j.semcancer.2007.06.009
  7. Maurer M, Loserth S, Kolb-Maurer A, et al (2002). A polymorphism in the human cytotoxic T-lymphocyte antigen 4 (CTLA4) gene (exon 1 +49) alters T-cell activation. Immunogenetics, 54, 1-8. https://doi.org/10.1007/s00251-002-0429-9
  8. Monne M, Piras G, Palmas A, Arru L, et al (2004). Cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism and susceptibility to non-Hodgkin's lymphoma. Am J Hematol, 76, 14-8. https://doi.org/10.1002/ajh.20045
  9. Qi P, Ruan CP, Wang H, et al (2010). CTLA-4 +49A>G polymorphism is associated with the risk but not with the progression of colorectal cancer in Chinese. Int J Colorectal Dis, 25, 39-45. https://doi.org/10.1007/s00384-009-0806-z
  10. Rodriguez S, Gaunt T R and Day I. N. M. (2009) Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol, 169, 505-14.
  11. Shaukat U, Ismail M, Mehmood N (2013). Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population. Asian Pac J Cancer Prev, 14, 5625-9. https://doi.org/10.7314/APJCP.2013.14.10.5625
  12. Solerio E, Tappero G, Iannace L, et al (2005). CTLA4 gene polymorphism in Italian patients with colorectal adenoma and cancer. Dig Liver Dis, 37, 170-5. https://doi.org/10.1016/j.dld.2004.10.009
  13. Song B, Liu Y, Liu J, et al (2011). CTLA-4 +49A>G polymorphism is associated with advanced non-small cell lung cancer prognosis. Respiration, 82, 439-44. https://doi.org/10.1159/000329345
  14. Sun T, Zhou Y, Yang M, et al (2008). Functional genetic variations in cytotoxic T-lymphocyte antigen 4 and susceptibility to multiple types of cancer. Cancer Res, 68, 7025-34. https://doi.org/10.1158/0008-5472.CAN-08-0806
  15. Taheri NS, Bakhshandehnosrat S, Tabiei MN, et al (2012). Epidemiological pattern of breast cancer in Iranian women: is there an ethnic disparity? Asian Pac J Cancer Prev, 13, 4517-20. https://doi.org/10.7314/APJCP.2012.13.9.4517
  16. Geng R, Song F, Yang X, et al (2013). Association between cytotoxic T lymphocyte antigen-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk: a meta-analysis. Tumour Biol. [Epub ahead of print]
  17. Chistiakov DA, Savost'anov KV, Turakulov RI, et al (2006). Genetic analysis and functional evaluation of the C/T (-318) and A/G(-1661) polymorphisms of the CTLA-4 gene inpatients affected with Graves' disease. Clin Immunol, 118, 233-42. https://doi.org/10.1016/j.clim.2005.09.017
  18. Dilmec F, Ozgonul A, Uzunkoy A, et al (2008). Investigation of CTLA-4 and CD28 gene polymorphisms in a group of Turkish patients with colorectal cancer. Int J Immunogenet, 35, 317-21. https://doi.org/10.1111/j.1744-313X.2008.00782.x
  19. Feng M, Zhang FB, Deng HR. et al (2013). The CTLA4 +49A/G polymorphism is associated with an increased risk of Hashimoto's thyroiditis in Asian but not Caucasian populations: an updated meta-analysis. Endocrine, 44, 350-8. https://doi.org/10.1007/s12020-013-0014-z
  20. Ghaderi A. (2011). CTLA4 gene variants in autoimmunity and cancer: a comparative review. Iran J Immunol, 8, 127-49.
  21. Ghaderi A, Yeganeh F, Kalantari T, et al (2004). Cytotoxic T lymphocyte antigen-4 gene in breast cancer. Breast Cancer Res Treat, 86, 1-7. https://doi.org/10.1023/B:BREA.0000032918.89120.8e
  22. Hou R, Cao B, Chen Z, et al (2010). Association of cytotoxic T lymphocyte-associated antigen-4 gene haplotype with the susceptibility to gastric cancer. Mol Biol Rep, 37, 515-20. https://doi.org/10.1007/s11033-009-9705-1
  23. Ligers A, Teleshova N, Masterman T, et al (2001). CTLA-4 gene expression is influenced by promoter and exon 1 polymorphisms. Genes Immun, 2, 145-52. https://doi.org/10.1038/sj.gene.6363752
  24. Mandal RK, Mittal T, Kapoor R, et al (2010). NER and BER repair gene polymorphisms in a healthy north Indian cohort and comparison with different ethnic groups worldwide. Asian Pac J Cancer Prev, 11, 1601-4.
  25. Blank CU (2014). The perspective of immunotherapy: new molecules and new mechanisms of action in immune modulation. Curr Opin Oncol, 26, 204-14 https://doi.org/10.1097/CCO.0000000000000054

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