Skip to main content
SpringerLink
Log in

Interferon gamma +874 T/A polymorphism increases the risk of cervical cancer: evidence from a meta-analysis

  • Research Article
  • Published:
Tumor Biology

Abstract

Data from previous studies about the association between interferon gamma (IFN-γ) +874 T/A (rs2430561) polymorphism and cervical cancer risk offer controversial results. To obtain a more dependable conclusion, this meta-analysis was performed. We selected eight articles including nine case–control studies with 1,116 cases and 1,290 controls, odds ratios (OR) with 95 % confidence intervals (CI) were used to assess the strength of the association. Subgroup analysis was carried out by ethnicity, source of controls, genotyping methods, and score of quality assessment. Our meta-analysis indicated that the IFN-γ (+874 T/A) polymorphism significantly increased the risk of cervical cancer in the codominant model (TA vs. TT: OR = 1.471, 95 % CI = 1.137–1.903, P = 0.003, I 2% = 0.0, P Q  = 0.785) and the dominant model (TA + AA vs. TT: OR = 1.399, 95 % CI = 1.097–1.784, P = 0.007, I 2% = 0.0, P Q  = 0.486) in the overall population. Stratified analysis by ethnicity indicated a significantly increased risk of cervical cancer in Asians in the codominant model (TA vs. TT: OR = 1.494, 95 % CI = 1.069–2.087, P = 0.019, I 2% = 0.0, P Q  = 0.440) and the dominant model (OR = 1.455, 95 % CI = 1.062–1.993, P = 0.019, I 2% = 42.9, P Q  = 0.154). Thus, the IFN-γ (+874 T/A) polymorphism is likely to increase the risk of cervical cancer. Because of the limited studies and sample sizes included in our meta-analysis, further well-designed and large-scale studies are demanded to confirm our results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002;97:72–81.

    Article  CAS  PubMed  Google Scholar 

  2. Schoell WM, Janicek MF and Mirhashemi R (1999) Epidemiology and biology of cervical cancer. Seminars in surgical oncology, Wiley Online Library, pp. 203–211

  3. Stanley M. HPV-immune response to infection and vaccination. Infect Agent Cancer. 2010;5:1–6.

    Article  Google Scholar 

  4. Kang S, Roh JW, Kim JW. Single nucleotide polymorphism: a new risk factor for endometrial cancer? Future Oncol. 2005;1:323–30.

    Article  CAS  PubMed  Google Scholar 

  5. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–64.

    Article  CAS  PubMed  Google Scholar 

  6. Motoyama S, Miura M, Hinai Y, Maruyama K, Usami S, Nakatsu T, et al. Interferon-gamma 874A > T genetic polymorphism is associated with infectious complications following surgery in patients with thoracic esophageal cancer. Surgery. 2009;146:931–8. doi:10.1016/j.surg.2009.04.034.

    Article  PubMed  Google Scholar 

  7. Srivastava RM, Lee SC, Andrade Filho PA, Lord CA, Jie HB, Davidson HC, et al. Cetuximab-activated natural killer and dendritic cells collaborate to trigger tumor antigen-specific T-cell immunity in head and neck cancer patients. Clin Cancer Res. 2013;19:1858–72. doi:10.1158/1078-0432.CCR-12-2426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schena FP, Cerullo G, Torres DD, Scolari F, Foramitti M, Amoroso A, et al. Role of interferon-γ gene polymorphisms in susceptibility to IgA nephropathy: a family-based association study. Eur J Hum Genet. 2006;14:488–96.

    Article  CAS  PubMed  Google Scholar 

  9. 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;39:7627–34. doi:10.1007/s11033-012-1597-9.

    Article  PubMed  Google Scholar 

  10. Fernandes AP, Goncalves MA, Simoes RT, Mendes-Junior CT, Duarte G, Donadi EA. A pilot case–control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions. Eur J Obstet Gynecol Reprod Biol. 2008;140:241–4. doi:10.1016/j.ejogrb.2008.04.007.

    Article  CAS  PubMed  Google Scholar 

  11. 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;116:1671–7. doi:10.1111/j.1471-0528.2009.02307.x.

    Article  CAS  PubMed  Google Scholar 

  12. Govan VA, Carrara HR, Sachs JA, Hoffman M, Stanczuk GA, Williamson A-L. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer. J Carcinog. 2003;2:3.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ivansson EL, Juko-Pecirep I, Gyllensten UB. Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer. Gynecol Oncol. 2010;116:544–8. doi:10.1016/j.ygyno.2009.10.084.

    Article  CAS  PubMed  Google Scholar 

  14. 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;30:224–9.

    CAS  PubMed  Google Scholar 

  15. Maskoen AM, Susanto H, Surialaga S, Sahiratmadja E. IFNG Polymorphism (+874 T > A) is not a risk factor for cervical cancer. Univ Med. 2013;32:29–36.

    Google Scholar 

  16. von Linsingen R, Bompeixe EP, Maestri CA, Carvalho NS, da Graca BM. IFNG (+874 T/A) polymorphism and cervical intraepithelial neoplasia in Brazilian women. J Interferon Cytokine Res. 2009;29:285–8. doi:10.1089/jir.2008.0081.

    Article  Google Scholar 

  17. 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;158:330–3. doi:10.1016/j.ejogrb.2011.05.019.

    Article  CAS  PubMed  Google Scholar 

  18. Kim JW, Roh JW, Park NH, Song YS, Kang SB, Lee HP. Interferon, alpha 17 (IFNA17) Ile184Arg polymorphism and cervical cancer risk. Cancer Lett. 2003;189:183–8.

    Article  CAS  PubMed  Google Scholar 

  19. 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;38:4461–7. doi:10.1007/s11033-010-0575-3.

    Article  CAS  PubMed  Google Scholar 

  20. Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, et al. Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol. 2005;162:201–11.

    Article  PubMed  Google Scholar 

  21. Ye X-H, Bu Z-B, Feng J, Peng L, Liao X-B, Zhu X-L, Sun X-l, Yu H-G, Yan D-F and Yan S-X (2013) Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis. Molecular biology reports:1–13.

  22. Higgins J, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  23. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ: Br Med J. 2003;327:557.

    Article  Google Scholar 

  24. Lee JE, Lee SJ, Namkoong SE, Um SJ, Sull JW, Jee SH, et al. Gene-gene and gene-environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer. Int J Gynecol Cancer. 2004;14:118–25.

    Article  CAS  PubMed  Google Scholar 

  25. Delaney NL, Esquenazi V, Lucas DP, Zachary AA, Leffell MS. TNF-alpha, TGF-beta, IL-10, IL-6, and INF-gamma alleles among African Americans and Cuban Americans. Report of the ASHI Minority Workshops: Part IV. Hum Immunol. 2004;65:1413–9. doi:10.1016/j.humimm.2004.07.240.

    Article  CAS  PubMed  Google Scholar 

  26. Poli F, Nocco A, Berra S, Scalamogna M, Taioli E, Longhi E, et al. Allele frequencies of polymorphisms of TNFA, IL‐6, IL‐10 and IFNG in an Italian Caucasian population. Eur J Immunogenet. 2002;29:237–40.

    Article  CAS  PubMed  Google Scholar 

  27. Pravica V, Perrey C, Stevens A, Lee J-H, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-γ gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-γ production. Hum Immunol. 2000;61:863–6.

    Article  CAS  PubMed  Google Scholar 

  28. Wang Z-E, Reiner SL, Zheng S, Dalton DK, Locksley RM. CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major. J Exp Med. 1994;179:1367–71.

    Article  CAS  PubMed  Google Scholar 

  29. Wiechec E, Hansen LL. The effect of genetic variability on drug response in conventional breast cancer treatment. Eur J Pharmacol. 2009;625:122–30. doi:10.1016/j.ejphar.2009.08.045.

    Article  CAS  PubMed  Google Scholar 

  30. Sarvari J, Norozian H, Fattahi MR, Pirbonyeh N, Moattari A. The role of interferon gamma gene polymorphism (+874A/T, +2109A/G, and -183G/T) in response to treatment among hepatitis C infected patients in Fars Province, Southern Iran. Hepat Mon. 2014;14:e14476. doi:10.5812/hepatmon.14476.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Oxenkrug G, Perianayagam M, Mikolich D, Requintina P, Shick L, Ruthazer R, et al. Interferon-gamma (+874) T/A genotypes and risk of IFN-alpha-induced depression. J Neural Transm. 2011;118:271–4. doi:10.1007/s00702-010-0525-1.

    Article  CAS  PubMed  Google Scholar 

  32. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ: Br Med J. 2001;323:101.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China

    Yifan Sun, Yu Lu, Qiliu Pen, Taijie Li, Li Xie & Yan Deng

  2. Department of Obstetrics and Gynecology and Reproductive center, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China

    Aiping Qin

Authors
  1. Yifan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiliu Pen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taijie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aiping Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aiping Qin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Y., Lu, Y., Pen, Q. et al. Interferon gamma +874 T/A polymorphism increases the risk of cervical cancer: evidence from a meta-analysis. Tumor Biol. 36, 4555–4564 (2015). https://doi.org/10.1007/s13277-015-3100-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3100-4

Keywords

Search

Navigation