Abstract
Interferon gamma (IFN-γ) plays a pivotal role in antiproliferative, antitumor and antiviral activities. The +874 polymorphism in IFN gene region reportedly affects cancer risk. However, pertinent studies offer conflicting results. To derive a more precise estimation, we performed a meta-analysis based on 1,929 cases and 2,830 controls from 17 published case–control studies, assessing the strength of the association using odds ratios with 95% confidence intervals. Our meta-analysis showed the evidence that IFN-γ +874 T/A was not associated with increased cancer risk in ethnicity and source of controls. However, stratified analysis by cancer type indicated a significantly increased risk of cervical cancer (AT vs. TT: OR = 1.10, 95% CI = 1.02–1.19, P = 0.961 for heterogeneity). Further prospective researches with a larger single study are required to evaluate any association with other types of cancer or in other populations.
Similar content being viewed by others
References
Song SH, Lee JK, Lee NW, Saw HS, Kang JS, Lee KW (2008) Interferon-gamma (IFN-gamma): a possible prognostic marker for clearance of high-risk human papillomavirus (HPV). Gynecol Oncol 108:543–548
Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264
Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto YXY (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21WAF1/CIP1 mediated by STAT1. Science 272:719–722
Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr (1996) Transcriptionally active Stat1 is required for the anti-proliferative effects of both interferon-α and interferon-γ. Proc Natl Acad Sci USA 93:7673–7678
Mandal M, Bandyopadhyay D, Goepfert TM, Kumar R (1998) Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK). Oncogene 16:217–225
Buard A, Vivo C, Monnet I, Boutin C, Pilatte Y, Jaurand MC (1998) Human malignant mesothelioma cell growth: activation of janus kinase 2 and signal transducer and activator of transcription 1α for inhibition by interferon-γ. Cancer Res 58:840–847
Chen B, He L, Savell VH, Jenkins JJ, Parham DM (2000) Inhibition of the interferon-γ/signal transducers and activators of transcription (STAT) pathway by hypermethylation at a STAT-binding site in the p21WAF1 promoter region. Cancer Res 60:3290–3298
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364
Folkman J (1999) Angiogenic zip code. Nat Biotechnol 17:749
Calvo J, Martínez N, Etxagibel A, Calleja S, Sáez-torres C, Sedeño M, Julià R, Muncunill J, Matamoros N, Gayà A (2002) Allelic frequencies of polymorphic variants of cytokine genes (IL1A, IL1B, IL1RN, IL6, IL10, IL12p40, and IFNG) in a Spanish population. Inmunologia 21(2):76–86
Pravica V, Asderakis A, Perrey C, Hajeer A, Sinnott PJ, Hutchison IV (1999) In vitro production of IFN-γ correlates with CA repeat polymorphism in the human IFN-γ gene. Eur J Immunogenet 26:1–3
Pravica V, Perrey C, Stevens A, Lee J-H, Hutchinson IV (2000) 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 61:863–866
Matos GI, Covas Cde J, Bittar Rde C, Gomes-Silva A, Marques F, Maniero VC, Amato VS, Oliveira-Neto MP, Mattos Mda S, Pirmez C, Sampaio EP, Moraes MO, Da-Cruz AM (2007) IFNγ +874 T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-gamma production. BMC Infect Dis 7:33
Horvath CM (2004) The Jak-STAT pathway stimulated by interferon gamma. Sci STKE 260:tr8
Gough DJ, Levy DE, Johnstone RW, Clarke CJ (2008) IFN gamma signaling-does it mean JAK-STAT? Cytokine Growth Factor Rev 19:383–394
Schena FP, Cerullo G, Torres DD, Scolari F, Foramitti M, Amoroso A, Pirulli D, Floege J, Mertens PR, Zerres K, Alexopoulos E, Kirmizis D, Zelante L, Bisceglia L (2006) Role of interferon-gamma gene polymorphisms in susceptibility to IgA nephropathy: a family-based association study. Eur J Hum Genet 14:488–496
Scola L, Vaglica M, Crivello A, Palmeri L, Forte GI, Macaluso MC, Giacalone A, Di Noto L, Bongiovanni A, Raimondi C, Accardo A, Verna R, Candore G, Caruso C, Lio D, Palmeri S (2006) Cytokine gene polymorphisms and breast cancer susceptibility. Ann NY Acad Sci 1089:104–109
Kamali-Sarvestani E, Merat A, Talei AR (2005) 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 223:113–119
Gonullu G, Basturk B, Evrensel T, Oral B, Gozkaman A, Manavoglu O (2007) Association of breast cancer and cytokine gene polymorphism in Turkish women. Saudi Med J 28:1728–1733
Gangwar R, Pandey S, Mittal RD (2009) Association of interferon-gamma +874 A polymorphism with the risk of developing cervical cancer in north-Indian population. BJOG 116:1671–1677
Kordi Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V (2008) Expression and polymorphism of IFN-gamma gene in patients with cervical cancer. Exp Oncol 30:224–229
Govan VA, Carrara HR, Sachs JA, Hoffman M, Stanczuk GA, Williamson AL (2003) Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer. J Carcinog 2:3
Nikolova PN, Pawelec GP, Mihailova SM (2007) Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population. Cancer Immunol Immunother 56:371–379
Howell WM, Turner SJ, Theaker JM, Bateman AC (2003) Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma. Eur J Immunogenet 30:409–414
Farhat K, Hassen E, Gabbouj S, Bouaouina N, Chouchane L (2008) Interleukin-10 and interferon-gamma gene polymorphisms in patients with nasopharyngeal carcinoma. Int J Immunogenet 35:197–205
Colakogullari M, Ulukaya E, Yilmaztepe Oral A, Aymak F, Basturk B, Ursavas A, Oral HB (2008) The involvement of IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish lung cancer patients. Cell Biochem Funct 26:283–290
Nearman ZP, Wlodarski M, Jankowska AM, Howe E, Narvaez Y, Ball E, Maciejewski JP (2007) Immunogenetic factors determining the evolution of T-cell large granular lymphocyte leukaemia and associated cytopenias. Br J Haematol 136:237–248
Baştürk B, Yavaşçaoğlu I, Vuruşkan H, Göral G, Oktay B, Oral HB (2005) Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma. Cytokine 30:41–45
Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, Yano K, Nagaoka S, Matsumoto T, Nakao K, Hamasaki K, Yatsuhashi H, Ishibashi H, Eguchi K (2005) Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection-association between TGF-beta1 polymorphisms and hepatocellular carcinoma. J Hepatol 42:505–510
Ahirwar DK, Agrahari A, Mandhani A, Mittal RD (2009) Cytokine gene polymorphisms are associated with risk of urinary bladder cancer and recurrence after BCG immunotherapy. Biomarkers 14:213–218
Talseth BA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott RJ (2007) Lack of association between genetic polymorphisms in cytokine genes and disease expression in patients with hereditary non-polyposis colorectal cancer. Scand J Gastroenterol 42:628–632
Talar-Wojnarowska R, Gasiorowska A, Smolarz B, Romanowicz-Makowska H, Kulig A, Malecka-Panas E (2009) Tumor necrosis factor alpha and interferon gamma genes polymorphisms and serum levels in pancreatic adenocarcinoma. Neoplasma 56:56–62
Der Simonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in metaanalysis detected by a simple, graphical test. BMJ 315:629–634
Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-c an overview of signals mechanisms and functions. J Leukoc Biol 75:163–189
Tartour E, Gey A, Sastre-Garau X, Lombard Surin I, Mosseri V, Fridman WH (1998) Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas. J Natl Cancer Inst 90:287–294
Gey A, Kumari P, Sambandam A, Lecuru F, Cassard L, Badoual C, Fridman C, Nagarajan B, Fridman WH, Tartour E (2003) Identification and characterization of a group of cervical carcinoma patients with profound downregulation of intratumoral Type 1 (IFN gamma) and Type 2 (IL-4) cytokine mRNA expression. Eur J Cancer 39:595–603
Tso HW, Ip WK, Chong WP, Tam CM, Chiang AK, Lau YL (2005) Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 6:358–363
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867
Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, Spitz MR (2000) Repair of tobacco carcinogen induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst 92:1764–1772
Author information
Authors and Affiliations
Corresponding authors
Additional information
Yuan-Yuan Mi, Qian-Qian Yu and Bin Xu have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Mi, YY., Yu, QQ., Xu, B. et al. Interferon gamma +874 T/A polymorphism contributes to cancer susceptibility: a meta-analysis based on 17 case–control studies. Mol Biol Rep 38, 4461–4467 (2011). https://doi.org/10.1007/s11033-010-0575-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-010-0575-3