The meta-analysis was conducted to evaluate the correlations between common
genetic polymorphisms in the IFN-γ gene and susceptibility to breast cancer. The
following electronic databases were searched without language restrictions: MEDLINE
(1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE (1980 ~ 2013),
CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical
Database (CBM) (1982 ~ 2013). Meta-analysis was performed with the use of the STATA
statistical software. Odds ratios (OR) with their 95 % confidence intervals (95 %
CIs) were calculated. Nine clinical case-control studies met all the inclusion
criteria and were included in this meta-analysis. A total of 1,182 breast cancer
patients and 1,525 healthy controls were involved in this meta-analysis. Three
functional polymorphisms were assessed, including rs2069705 C>T, rs2430561
T>A, and CA repeats 2/X. Our meta-analysis results indicated that IFN-γ genetic
polymorphisms might be significantly associated with an increased risk of breast
cancer (allele model: OR = 1.37, 95 % CI = 1.03 ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37,
P = 0.046; homozygous model: OR = 2.23, 95 %
CI = 1.30 ~ 3.82, P = 0.004; respectively),
especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity
suggested that genetic polymorphisms in the IFN-γ gene were closely
correlated with increased breast cancer risk among Asians (allele model: OR = 1.21,
95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model:
OR = 3.44, 95 % CI = 2.07 ~ 5.71, P < 0.001;
recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025; homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80,
P = 0.006; respectively), but not among
Caucasians (all P > 0.05). Our meta-analysis
supported the hypothesis that IFN-γ genetic polymorphisms may contribute to an increased
risk of breast cancer, especially the rs2430561 T>A polymorphism among
IFN-γGenetic polymorphism Susceptibility Breast cancer Meta-analysis
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This work was supported by the Natural Science Foundation of Heilongjiang
Province (No. D201166). We would like to acknowledge the reviewers for their helpful
comments on this paper.
Conflicts of interest
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global
cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
Guo LJ, Zhang QY. Decreased serum miR-181a is a potential new tool
for breast cancer screening. Int J Mol Med. 2012;30(3):680–6.PubMedGoogle Scholar
Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G.
Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical
care system database. Breast Cancer Res Treat.
Nickels S, Truong T, Hein R, Stevens K, Buck K, Behrens S, et al.
Evidence of gene-environment interactions between common breast cancer
susceptibility loci and established environmental risk factors. PLoS Genet.
La Vecchia C, Giordano SH, Hortobagyi GN, Chabner B. Overweight,
obesity, diabetes, and risk of breast cancer: interlocking pieces of the puzzle.
Oncologist. 2011;16(6):726–9.PubMedCentralCrossRefPubMedGoogle Scholar
Park SK, Kim Y, Kang D, Jung EJ, Yoo KY. Risk factors and control
strategies for the rapidly rising rate of breast cancer in Korea. J Breast
Cancer. 2011;14(2):79–87.PubMedCentralCrossRefPubMedGoogle Scholar
Fontein DB, de Glas NA, Duijm M, Bastiaannet E, Portielje JE, Van
de Velde CJ, et al. Age and the effect of physical activity on breast cancer
survival: a systematic review. Cancer Treat Rev.
Reiner AS, John EM, Brooks JD, Lynch CF, Bernstein L, Mellemkjaer
L, et al. Risk of asynchronous contralateral breast cancer in noncarriers of
BRCA1 and BRCA2 mutations with a family history of breast cancer: a report from
the Women’s Environmental Cancer and Radiation Epidemiology Study. J Clin Oncol.
Bouchardy C, Rapiti E, Fioretta G, Schubert H, Chappuis P, Vlastos
G, et al. Impact of family history of breast cancer on tumour characteristics,
treatment, risk of second cancer and survival among men with breast cancer.
Swiss Med Wkly. 2013;143:w13879.PubMedGoogle Scholar
Su Y, Tang LY, Chen LJ, He JR, Su FX, Lin Y, et al. Joint effects
of febrile acute infection and an interferon-gamma polymorphism on breast cancer
risk. PLoS One. 2012;7(5):e37275.PubMedCentralCrossRefPubMedGoogle Scholar
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
Kim K, Cho SK, Sestak A, Namjou B, Kang C, Bae SC. Interferon-gamma
gene polymorphisms associated with susceptibility to systemic lupus
erythematosus. Ann Rheum Dis. 2010;69(6):1247–50.CrossRefPubMedGoogle Scholar
He JR, Chen LJ, Su Y, Cen YL, Tang LY, Yu DD, et al. Joint effects
of Epstein-Barr virus and polymorphisms in interleukin-10 and interferon-gamma
on breast cancer risk. J Infect Dis. 2012;205(1):64–71.CrossRefPubMedGoogle Scholar
Chou SF. Development of a manual self-assembled colloidal gold
nanoparticle-immunochromatographic strip for rapid determination of human
interferon-gamma. Analyst. 2013;138(9):2620–3.CrossRefPubMedGoogle Scholar
Pluddemann A, Mukhopadhyay S, Gordon S. Innate immunity to
intracellular pathogens: macrophage receptors and responses to microbial entry.
Immunol Rev. 2011;240(1):11–24.CrossRefPubMedGoogle Scholar
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
Erdei E, Kang H, Meisner A, White K, Pickett G, Baca C, et al.
Polymorphisms in cytokine genes and serum cytokine levels among New Mexican
women with and without breast cancer. Cytokine.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the
assessment of the quality of nonrandomized studies in meta-analyses. Eur J
Epidemiol. 2010;25(9):603–5.CrossRefPubMedGoogle Scholar
Zintzaras E, Ioannidis JP. HEGESMA: genome search meta-analysis and
heterogeneity testing. Bioinformatics. 2005;21(18):3672–3.CrossRefPubMedGoogle Scholar
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of
two methods to detect publication bias in meta-analysis. JAMA.
Wu GH, Zhang JY, Lu PX. Association of single nucleotide
polymorphism of interferon-ganuna gene+874 site and breast cancer. Cancer Res
Prev Treat. 2008;35(9).Google Scholar
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
Wu JM, Bensen-Kennedy D, Miura Y, Thoburn CJ, Armstrong D,
Vogelsang GB, et al. The effects of interleukin 10 and interferon gamma cytokine
gene polymorphisms on survival after autologous bone marrow transplantation for
patients with breast cancer. Biol Blood Marrow Transplant.
Saha A, Dhir A, Ranjan A, Gupta V, Bairwa N, Bamezai R. Functional
IFNG polymorphism in intron 1 in association with an increased risk to promote
sporadic breast cancer. Immunogenetics. 2005;57(3–4):165–71.CrossRefPubMedGoogle Scholar
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.
Farrell RA, Antony D, Wall GR, Clark DA, Fisniku L, Swanton J, et
al. Humoral immune response to EBV in multiple sclerosis is associated with
disease activity on MRI. Neurology. 2009;73(1):32–8.PubMedCentralCrossRefPubMedGoogle Scholar
Wingate PJ, McAulay KA, Anthony IC, Crawford DH. Regulatory T cell
activity in primary and persistent Epstein-Barr virus infection. J Med Virol.
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.