Advertisement

Tumor Biology

, Volume 35, Issue 7, pp 6405–6414 | Cite as

Lack of association between interferon gamma +874 T/A polymorphism and cancer risk: an updated meta-analysis

  • Yu-Zheng Ge
  • Yi-Dan Wang
  • Zheng Xu
  • Lu-Wei Xu
  • Ya-Ping Wang
  • Mao-Hong Gu
  • Ai-Xing Ding
  • Xian-Bo Zhu
  • Ran Wu
  • Wen-Cheng Li
  • You-Di Xu
  • Rui-Peng Jia
Research Article

Abstract

Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele—OR = 0.96, 95 % CI, 0.86–1.08), homozygote comparison (AA vs. TT—OR = 0.97, 95 % CI, 0.79–1.21), heterozygote comparison (AT vs. TT—OR = 1.03, 95 % CI, 0.87–1.23), dominant model (AA + AT vs. TT—OR = 1.00, 95 % CI, 0.87–1.15), nor recessive model (AA vs. AT + TT—OR = 0.93, 95 % CI, 0.78–1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy–Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT—OR = 0.68, 95 % CI, 0.47–0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.

Keywords

Interferon gamma Polymorphism Cancer Meta-analysis 

Notes

Acknowledgments

This project was supported by grants from the National Natural Science Foundation of China (81070597 and 81370853), Science and Education Development Program of the Jiangsu Province Health Board (LJ201107), Six Talent Peaks of the Jiangsu Province Health Bureau (2011-WS-093), and Research and Innovation Program for Graduates of Jiangsu Province (CXZZ13_0583).

Conflict of interest

None.

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefPubMedGoogle Scholar
  3. 3.
    Jin P, Panelli MC, Marincola FM, Wang E. Cytokine polymorphism and its possible impact on cancer. Immunol Res. 2004;30(2):181–90.CrossRefPubMedGoogle Scholar
  4. 4.
    Howell WM, Rose-Zerilli MJ. Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutr. 2007;137(1 Suppl):194S–9S.PubMedGoogle Scholar
  5. 5.
    Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75(2):163–89.CrossRefPubMedGoogle Scholar
  6. 6.
    Billiau A, Matthys P. Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev. 2009;20(2):97–113.CrossRefPubMedGoogle Scholar
  7. 7.
    Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol. 2007;96:41–101.CrossRefPubMedGoogle Scholar
  8. 8.
    Zaidi MR, Merlino G. The two faces of interferon-gamma in cancer. Clin Cancer Res. 2011;17(19):6118–24.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Bekisz J, Sato Y, Johnson C, Husain SR, Puri RK, Zoon KC. Immunomodulatory effects of interferons in malignancies. J Interferon Cytokine Res. 2013;33(4):154–61.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol. 2000;61(9):863–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Dmitrienko S, Hoar DI, Balshaw R, Keown PA. Immune response gene polymorphisms in renal transplant recipients. Transplantation. 2005;80(12):1773–82.CrossRefPubMedGoogle Scholar
  12. 12.
    Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG. Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet. 2003;361(9372):1871–2.CrossRefPubMedGoogle Scholar
  13. 13.
    Skerrett DL, Moore EM, Bernstein DS, Vahdat L. Cytokine genotype polymorphisms in breast carcinoma: associations of TGF-beta1 with relapse. Cancer Invest. 2005;23(3):208–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Kamali-Sarvestani E, Merat A, Talei AR. Polymorphism in the genes of alpha and beta tumor necrosis factors (TNF-alpha and TNF-beta) and gamma interferon (IFN-gamma) among Iranian women with breast cancer. Cancer Lett. 2005;223(1):113–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Scola L, Vaglica M, Crivello A, Palmeri L, Forte GI, Macaluso MC, et al. Cytokine gene polymorphisms and breast cancer susceptibility. Ann N Y Acad Sci. 2006;1089:104–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Gonullu G, Basturk B, Evrensel T, Oral B, Gozkaman A, Manavoglu O. Association of breast cancer and cytokine gene polymorphism in Turkish women. Saudi Med J. 2007;28(11):1728–33.PubMedGoogle Scholar
  17. 17.
    Karakus N, Kara N, Ulusoy AN, Ozaslan C, Bek Y. Tumor necrosis factor alpha and beta and interferon gamma gene polymorphisms in Turkish breast cancer patients. DNA Cell Biol. 2011;30(6):371–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Wu G, Zhang J, Lu P. Association of single nucleotide polymorphism of interferon-gamma gene +874 site and breast cancer. Zhong Liu Fang Zhi Za Zhi. 2008;35(9):651–70.Google Scholar
  19. 19.
    Govan VA, Carrara HR, Sachs JA, Hoffman M, Stanczuk GA, Williamson AL. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer. J Carcinog. 2003;2(1):3.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Guzman VB, Yambartsev A, Goncalves-Primo A, Silva ID, Carvalho CR, Ribalta JC, et al. New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer. Hum Mol Genet. 2008;17(12):1838–44.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Gangwar R, Pandey S, Mittal RD. Association of interferon-gamma +874A polymorphism with the risk of developing cervical cancer in north-Indian population. BJOG. 2009;116(12):1671–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Ivansson EL, Juko-Pecirep I, Gyllensten UB. Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer. Gynecol Oncol. 2010;116(3):544–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang Q, Zhang C, Walayat S, Chen HW, Wang Y. Association between cytokine gene polymorphisms and cervical cancer in a Chinese population. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):330–3.CrossRefPubMedGoogle Scholar
  24. 24.
    do Carmo Vasconcelos de Carvalho V, de Macedo JL, de Lima CA, da Conceicao Gomes de Lima M, de Andrade Heraclio S, Amorim M, et al. IFN-gamma and IL-12B polymorphisms in women with cervical intraepithellial neoplasia caused by human papillomavirus. Mol Biol Rep. 2012;39(7):7627–34.CrossRefPubMedGoogle Scholar
  25. 25.
    Kordi Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V. Expression and polimorphism of IFN-gamma gene in patients with cervical cancer. Exp Oncol. 2008;30(3):224–9.PubMedGoogle Scholar
  26. 26.
    Wu G, Zhang J, Zuo W. Association between single nucleotide polymorphism of interferon-gamma gene +874 site and susceptibility to ovarian cancer. Journal of Jilin University Medicine Edition. 2009;35(3):507–10.Google Scholar
  27. 27.
    Amirzargar AA, Bagheri M, Ghavamzadeh A, Alimoghadam K, Khosravi F, Rezaei N, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet. 2005;32(3):167–71.CrossRefPubMedGoogle Scholar
  28. 28.
    Nearman ZP, Wlodarski M, Jankowska AM, Howe E, Narvaez Y, Ball E, et al. Immunogenetic factors determining the evolution of T-cell large granular lymphocyte leukaemia and associated cytopenias. Br J Haematol. 2007;136(2):237–48.CrossRefPubMedGoogle Scholar
  29. 29.
    Urbanowicz I, Mazur G, Stacherzak-Pawlik J, Bogunia-Kubik K, Wrobel T, Wozniak M, et al. IFN gamma gene polymorphism may contribute to the susceptibility to CLL. Pathol Oncol Res. 2010;16(2):213–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Basturk B, Evke E, Tunali A, Karakus S. Interleukin-10 and interferon-gamma cytokine gene polymorphisms may be risk factors for chronic myelogenous leukemia. Turkish Journal of Haematology. 2005;22(4):191–6.Google Scholar
  31. 31.
    Basturk B, Evke E, Karakus S, Tunali A. Potential risk factor of interleukin-10 gene polymorphism in acute myelogenous leukemia. UHOD-Uluslararasi Hematoloji-Onkoloji Dergisi. 2005;15(2):57–62.Google Scholar
  32. 32.
    Li J, Cao F, Tang H, Liu X, Zhou J. Study on plasma IFN-gamma expression levels and IFN-gamma polymorphism in patients with acute promyeiocyti leukemia. Zhong Guo You Sheng Yu Yi Chuan Za Zhi. 2008;16(2):39–40.Google Scholar
  33. 33.
    Andrie E, Michos A, Kalampoki V, Pourtsidis A, Moschovi M, Polychronopoulou S, et al. Genetic variants in immunoregulatory genes and risk for childhood lymphomas. Eur J Haematol. 2009;83(4):334–42.CrossRefPubMedGoogle Scholar
  34. 34.
    Howell WM, Turner SJ, Theaker JM, Bateman AC. Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma. Eur J Immunogenet. 2003;30(6):409–14.CrossRefPubMedGoogle Scholar
  35. 35.
    Nikolova PN, Pawelec GP, Mihailova SM, Ivanova MI, Myhailova AP, Baltadjieva DN, et al. Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population. Cancer Immunol Immunother. 2007;56(3):371–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Rizzato C, Canzian F, Rudnai P, Gurzau E, Stein A, Koppova K, et al. Interaction between functional polymorphic variants in cytokine genes, established risk factors and susceptibility to basal cell carcinoma of skin. Carcinogenesis. 2011;32(12):1849–54.CrossRefPubMedGoogle Scholar
  37. 37.
    Basturk B, Yavascaoglu I, Vuruskan H, Goral G, Oktay B, Oral HB. Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma. Cytokine. 2005;30(1):41–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Omrani M, Bazargani S, Bageri M. Interlukin-10, interferon-(gamma) and tumor necrosis factor-(alpha) genes variation in prostate cancer and benign prostatic hyperplasia. Current Urology. 2008;2(4):175–80.CrossRefGoogle Scholar
  39. 39.
    Ahirwar DK, Agrahari A, Mandhani A, Mittal RD. Cytokine gene polymorphisms are associated with risk of urinary bladder cancer and recurrence after BCG immunotherapy. Biomarkers. 2009;14(4):213–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Nieters A, Yuan JM, Sun CL, Zhang ZQ, Stoehlmacher J, Govindarajan S, et al. Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association. Cancer. 2005;103(4):740–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, et al. Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection—association between TGF-beta1 polymorphisms and hepatocellular carcinoma. J Hepatol. 2005;42(4):505–10.CrossRefPubMedGoogle Scholar
  42. 42.
    Teixeira AC, Mendes Jr CT, Marano LA, Deghaide NH, Secaf M, Elias Jr J, et al. Alleles and genotypes of polymorphisms of IL-18, TNF-alpha and IFN-gamma are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil. Hum Immunol. 2013;74(8):1024–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Talseth BA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott RJ. Lack of association between genetic polymorphisms in cytokine genes and disease expression in patients with hereditary non-polyposis colorectal cancer. Scand J Gastroenterol. 2007;42(5):628–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Fei B, Lv H, Chen Y, Yang J. Single nucleotide polymorphism of interferon-gamma gene +874 T/A in colorectal cancer. World Chin J Digestol. 2006;14(20):2022–5.Google Scholar
  45. 45.
    Du W, Ye W, Chen M, Li D, Jing X. Association research between polymorphism of IFN-gamma and IL-10, environmental risk factors, and susceptibility to esophageal cancer. Wei Sheng Yan Jiu. 2013;42(5):770–6.PubMedGoogle Scholar
  46. 46.
    Talar-Wojnarowska R, Gasiorowska A, Smolarz B, Romanowicz-Makowska H, Kulig A, Malecka-Panas E. Tumor necrosis factor alpha and interferon gamma genes polymorphisms and serum levels in pancreatic adenocarcinoma. Neoplasma. 2009;56(1):56–62.CrossRefPubMedGoogle Scholar
  47. 47.
    Farhat K, Hassen E, Gabbouj S, Bouaouina N, Chouchane L. Interleukin-10 and interferon-gamma gene polymorphisms in patients with nasopharyngeal carcinoma. Int J Immunogenet. 2008;35(3):197–205.CrossRefPubMedGoogle Scholar
  48. 48.
    Tai SH, Wei YS, Wang P, Zhou B, Ran P, Yang ZH, et al. Genetic polymorphisms of interferon-gamma and interleukin-8 in patients with nasopharyngeal carcinoma. Sichuan Da Xue Xue Bao Yi Xue Ban. 2007;38(5):862–5.PubMedGoogle Scholar
  49. 49.
    Colakogullari M, Ulukaya E, Yilmaztepe Oral A, Aymak F, Basturk B, Ursavas A, et al. The involvement of IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish lung cancer patients. Cell Biochem Funct. 2008;26(3):283–90.CrossRefPubMedGoogle Scholar
  50. 50.
    Mi YY, Yu QQ, Xu B, Zhang LF, Min ZC, Hua LX, et al. Interferon gamma +874 T/A polymorphism contributes to cancer susceptibility: a meta-analysis based on 17 case-control studies. Mol Biol Rep. 2011;38(7):4461–7.CrossRefPubMedGoogle Scholar
  51. 51.
    Liu F, Li B, Wei YG, Chen X, Ma Y, Yan LN, et al. IFN-gamma +874 A/T polymorphism and cancer risk: an updated analysis based on 32 case-control studies. Cytokine. 2011;56(2):200–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Ge YZ, Wu R, Jia RP, Liu H, Yu P, Zhao Y, et al. Association between interferon gamma +874 T > A polymorphism and acute renal allograft rejection: evidence from published studies. Mol Biol Rep. 2013;40(10):6043–51.CrossRefPubMedGoogle Scholar
  54. 54.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMedGoogle Scholar
  56. 56.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  57. 57.
    Wang BS, Liu Z, Xu WX, Sun SL. CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression. Tumour Biol. 2013;34(4):2357–66.CrossRefPubMedGoogle Scholar
  58. 58.
    Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J. A method for meta-analysis of molecular association studies. Stat Med. 2005;24(9):1291–306.CrossRefPubMedGoogle Scholar
  59. 59.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.CrossRefPubMedGoogle Scholar
  60. 60.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Slattery ML, Lundgreen A, Bondurant KL, Wolff RK. Interferon-signaling pathway: associations with colon and rectal cancer risk and subsequent survival. Carcinogenesis. 2011;32(11):1660–7.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yu-Zheng Ge
    • 1
  • Yi-Dan Wang
    • 2
  • Zheng Xu
    • 1
  • Lu-Wei Xu
    • 1
  • Ya-Ping Wang
    • 2
  • Mao-Hong Gu
    • 2
  • Ai-Xing Ding
    • 3
  • Xian-Bo Zhu
    • 3
  • Ran Wu
    • 1
  • Wen-Cheng Li
    • 1
  • You-Di Xu
    • 2
  • Rui-Peng Jia
    • 1
  1. 1.Department of Urology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
  2. 2.Department of Obstetrics and Gynecology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
  3. 3.Department of General Surgery, Nanjing First HospitalNanjing Medical UniversityNanjingChina

Personalised recommendations