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Asian Pacific Journal of Cancer Prevention : APJCP logoLink to Asian Pacific Journal of Cancer Prevention : APJCP
. 2020 Sep;21(9):2507–2515. doi: 10.31557/APJCP.2020.21.9.2507

Association between IL-27 Gene Polymorphisms and Cancer Susceptibility in Asian Population: A Meta-Analysis

Abdolkarim Moazeni-Roodi 1,2, Mohammad Hashemi 3,4,*, Saeid Ghavami 2,5,6,*
PMCID: PMC7779426  PMID: 32986346

Abstract

Background:

Interleukin 27 (IL-27) has potent antitumor activity. Several epidemiological studies have designated that genetic variants of the IL-27 gene may contribute to various cancer susceptibility, but the data were inconclusive.

Objective:

The current meta-analysis aimed to address the association between IL-27 rs153109, rs17855750, and rs181206 polymorphisms and the risk of cancer.

Data Sources:

Our team has selected eligible studies up to May 1, 2020, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases.

Results:

Our meta-analysis revealed that the carriers rs153109 A>G polymorphism in the IL-27 gene have higher risks of diseases in the heterozygous (OR=1.26, 95%CI=1.06-1.49, P=0.007, AG vs AA), homozygous (OR=1.18, 95%CI=1.01-1.37, p=0.33, GG vs AA), dominant (OR=1.25, 95%CI=1.07-1.47, P=0.006, AG+GG vs AA), and allele (OR=1.15, 95%CI=1.04-1.27, P=0.008, G vs A) genetic models. Stratified analysis by cancer type indicated that this variant was significantly associated with gastrointestinal cancer, colorectal cancer and breast cancer. The findings did not support an association between rs17855750 T>G, rs181206 T>C polymorphisms of IL-27 and cancer risk.

Conclusion:

the current study findings suggest that IL-27 rs153109 polymorphism significantly increased the risk of cancer susceptibility. Well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities is required to verify the findings.

Key Words: IL-27, polymorphism, cancer, meta-analysis

Introduction

Cancer, a major public health concern, remains a leading cause of morbidity and mortality worldwide (Siegel et al., 2015). While the etiologies of cancer is complicated and not fully understood, growing evidences indicating that a complex interaction between genetic and environmental factors involved in cancer development (Lichtenstein et al., 2000).

Interleukin-27 (IL-27), belonging to the IL-12 family, is a heterodimeric cytokine comprising of two subunits, 1L-27p28 and the Epstein-Barr virus-induced gene 3 protein (EBI3), and is generally secreted by activated antigen-presenting cells (Devergne et al., 1996; Liu et al., 2008). The human Il-27 gene (IL-27P28) is located on chromosome 16 (16p11) (Pflanz et al., 2002). It is well-known that IL-27 possesses antitumor activities against a variety of tumor types (Nagai et al., 2010; Di Carlo et al., 2014; Yoshida and Hunter, 2015; Yoshimoto et al., 2015). IL-27 is a polymorphic gene and several studies examined the association between IL-27 gene polymorphisms and risk of various cancers including, non-small-cell lung cancer (NSCLC) (Ge and Xiao, 2016), acute lymphoblastic leukemia (ALL) (Ghavami et al., 2018), nasopharyngeal carcinoma (NPC) (Wei et al., 2009; Pan et al., 2012), colorectal cancer (CRC) (Guo et al., 2012; Huang et al., 2012; Lyu et al., 2015), prostate cancer (PCa) (Munretnam et al., 2014), papillary thyroid carcinoma (PTC) (Zhang et al., 2015; Nie et al., 2017), hepatocellular carcinoma (HCC) (Peng et al., 2013), renal cell carcinoma (RCC) (Pu et al., 2015), osteosarcoma (Tang et al., 2014), esophageal cancer (Tao et al., 2012), cervical cancer (Wang et al., 2016), endometrial cancer (Yu et al., 2016), ovarian cancer (Zhang et al., 2014b), breast cancer (Zhang et al., 2014a), glioma (Zhao et al., 2009), and bladder cancer (Zhou et al., 2015). However, the findings of these studies have been controversial. So we conducted the present meta-analysis of eligible published studies to further assess the association between the IL-27 polymorphisms and cancer risk.

Materials and Methods

Identification of Eligible Studies

Two authors independently carried out a systematic literature search in PubMed, Web of Knowledge, and Scopus for all related reports using the key words “IL-27 or IL27 or interleukin 27” and “polymorphism or SNP or variation” and “cancer or tumor or carcinoma or malignancy or neoplasm”. The last search was updated on March 04, 2019.

Inclusion and Exclusion Criteria

Studies were implemented in the current meta-analysis if they met all of the criteria: (1) Assessment of the relationship between IL-27 gene polymorphisms and cancer susceptibility; (2) Case–control studies; (3) Adequate data to estimate pooled ORs with a 95% CIs. The exclusion criteria were: (1) not a case–control study, reviews, case reports, meta-analysis, and comments; (2) duplicate publication; (3) studies with insufficient data.

Data extraction

The data extraction from the eligible studies was achieved independently by two researchers according to the inclusion and exclusion criteria mentioned above. In each study, the following items were collected from each study: first author’s name, publication year, country, ethnicity, cancer type, source of controls, total number of cases and controls, genotype distributions of cases and controls, and Hardy-Weinberg equilibrium (HWE), respectively.

Statistical analysis

All statistical analyses were achieved using Stata, version 14.1 (Stata Corporation, College Station, TX, USA).

The HWE was evaluated for each study by the chi-square test in the control group. Pooled ORs and corresponding 95%CIs were calculated to estimate the strength of association between IL-27 gene polymorphism and cancer risk. The significance of the pooled OR was determined by Z test, in which p-value less than 0.05 was considered statistically significant.

The Q statistic test was used to check the heterogeneity among studies included in the meta-analysis. A p>0.10 indicated a lack of heterogeneity among studies, consequently the fixed effect model was used to calculate pooled OR. Otherwise, a random effects model was utilized.

Publication bias was evaluated by Begg’s funnel plot qualitatively, and Begg’s and Egger’s tests quantitatively. P-value less than 0.05 considered significant publication bias.

Sensitivity analysis was done by removing each study in turn to measure the results stability.

Results

Study Characteristics

In the current study, according to the inclusion and exclusion criteria, ultimately 20 case-control studies included in the meta-analysis. For rs153109, 21 studies containing 6,331 cases and 7,287 controls for were included in the quantitative analysis. Regarding rs17855750 variant, 4,023 cases and 4,671 controls from 14 studies and for rs181206 polymorphism, 2,078 cases and 2,242 controls from were 7 studies were included in the meta-analysis. The characteristics of the included studies are summarized in Table 1, Table 2 and Table 3.

Table 1.

Characteristics of All Studies Included in the Meta-Analysis for IL-27 rs153109 Polymorphism

Author Year Country Ethnicity Cancer type Source of control Genotyping Method Case/ control Cases Controls HWE
rs153109 (-964 A>G) AA AG GG A G AA AG GG A G
Fathi Maroufi 2018 Iran Asian Breast cancer HB PCR-RFLP 140/140 53 67 20 173 107 59 66 15 184 96 0.585
Ge 2016 China Asian NSCLC HB PCR-RFLP 388/390 115 219 54 449 327 129 213 48 471 309 0.005
Ghavami 2018 Iran Asian ALL HB PCR-RFLP 200/210 60 136 4 256 144 141 57 12 339 81 0.063
Guo 2012 China Asian CRC HB PCR-RFLP 170/160 53 84 33 190 150 75 66 19 216 104 0.449
Huang 2012 China Asian CRC HB PCR-RFLP 410/450 151 213 46 515 305 183 222 45 588 312 0.059
Lyu 2015 China Asian CRC HB PCR-RFLP 600/600 217 243 140 677 523 272 201 127 745 455 <0.001
Munretnam 2014 Malaysian Asian Prostate cancer HB Illumina’s 51/51 48 3 - - 37 14 - - -
Nie 2016 China Asian PTC HB PCR-RFLP 496/629 176 252 68 604 388 279 266 84 824 434 0.107
Pan 2012 China Asian NPC HB PCR-RFLP 190/200 90 78 22 258 122 85 87 28 257 143 0.453
Peng 2013 China Asian HCC HB PCR-RFLP 107/105 38 48 21 124 90 40 46 19 126 84 0.371
Pu 2015 China Asian RCC HB PCR-RFLP 329/386 129 154 46 412 246 196 145 45 537 235 0.026
Tang 2014 China Asian Osteosarcoma HB PCR-RFLP 160/250 56 85 19 197 123 100 124 26 324 176 0.168
Tao 2012 China Asian ESC HB PCR-RFLP 426/432 163 205 58 531 321 162 219 51 543 321 0.075
Wang 2016 China Asian CRC HB PCR-RFLP 380/380 257 80 43 594 166 232 92 56 556 204 <0.001
Wei 2009 China Asian NPC HB PCR-RFLP 302/310 119 150 33 388 216 113 161 36 387 233 0.06
Yu 2016 China Asian Endometrial HB PCR-RFLP 272/320 103 132 37 338 206 161 124 35 446 194 0.139
Zhang 2014 China Asian Ovarian cancer HB PCR-RFLP 229/320 85 103 41 273 185 161 124 35 446 194 0.139
Zhang 2014 China Asian Breast cancer HB PCR-RFLP 326/460 143 156 27 442 210 185 223 52 593 327 0.213
Zhang 2015 China Asian PTC HB PCR-RFLP 664/827 287 309 68 883 445 332 399 96 1063 591 0.147
Zhao 2009 China Asian Glioma HB PCR-RFLP 210/220 79 101 30 259 161 81 112 27 274 166 0.216
Zhou 2015 China Asian Bladder cancer HB PCR-RFLP 332/499 127 160 45 414 250 229 204 66 662 336 0.058
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Table 2.

Characteristics of All Studies Included in the Meta-Analysis for IL-27 rs17855750 Polymorphism

Author Year Country Ethnicity Cancer type Source of control Genotyping Method Case/ Cases Controls HWE
control
rs17855750 (2905 T>G) TT TG GG T G TT TG GG T G
Ghavami 2018 Iran Asian ALL HB PCR-RFLP 200/210 34 157 9 225 175 71 124 15 266 154 <0.001
Guo 2012 China Asian CRC HB PCR-RFLP 170/160 120 41 9 281 59 122 33 5 277 43 0.151
Huang 2012 China Asian CRC HB PCR-RFLP 410/450 341 69 0 751 69 382 68 0 832 68 0.083
Nie 2016 China Asian PTC HB PCR-RFLP 496/629 382 104 10 868 124 532 96 1 1160 98 0.118
Peng 2013 China Asian HCC HB PCR-RFLP 107/105 83 21 3 187 27 72 28 5 172 38 0.304
Pu 2015 China Asian RCC HB PCR-RFLP 329/386 255 64 10 574 84 327 59 0 713 59 0.104
Tang 2014 China Asian Osteosarcoma HB PCR-RFLP 160/250 132 28 0 292 28 205 45 0 455 45 0.118
Tao 2012 China Asian ESC HB PCR-RFLP 426/432 345 81 0 771 81 355 77 0 787 77 0.042
Wang 2016 China Asian cervical cancer HB PCR-RFLP 380/380 258 76 46 592 168 182 118 80 482 278 <0.001
Wei 2009 China Asian NPC HB PCR-RFLP 302/310 247 55 0 549 55 259 51 0 569 51 0.115
Yu 2016 China Asian endometrial HB PCR-RFLP 272/320 236 33 3 505 39 267 53 0 587 53 0.106
Zhang 2014 China Asian Ovarian cancer HB PCR-RFLP 229/320 170 51 8 391 67 267 53 0 587 53 0.106
Zhao 2009 China Asian Glioma HB PCR-RFLP 210/220 169 41 0 379 41 185 35 0 405 35 0.2
Zhou 2015 China Asian Breast cancer HB PCR-RFLP 332/499 275 53 4 603 61 421 78 0 920 78 0.058
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ALL, acute lymphoblastic leukemia; CRC, Colorectal cancer; ESC, esophageal cancer; PTC, papillary thyroid carcinoma; NPC, nasopharyngeal carcinoma; HCC, hepatocellular carcinoma; RCC, Renal cell carcinoma; HB, Hospital-based.

Table 3.

Characteristics of all studies included in the meta-analysis for IL-27 rs181206 polymorphism

Author Year Country Ethnicity Cancer type Source of control Genotyping Method Case/ control Cases Controls HWE
rs181206 (4730 T>C) TT TC CC T C TT TC CC T C
Huang 2012 China Asian CRC HB PCR-RFLP 410/450 331 79 0 741 79 373 77 0 823 77 0.047
Pan 2012 China Asian NPC HB PCR-RFLP 190/200 157 33 0 347 33 158 42 0 358 42 0.097
Tang 2014 China Asian Osteosarcoma HB PCR-RFLP 160/250 131 29 0 291 29 207 43 0 457 43 0.137
Tao 2012 China Asian ESC HB PCR-RFLP 426/432 335 91 0 761 91 354 78 0 786 78 0.039
Wang 2016 China Asian Cervical cancer HB PCR-RFLP 380/380 226 92 62 544 216 192 99 89 483 277 <0.001
Wei 2009 China Asian NPC HB PCR-RFLP 302/310 241 61 0 543 61 253 57 0 563 57 0.075
Zhao 2009 China Asian Glioma HB PCR-RFLP 210/220 166 44 0 376 44 182 38 0 402 38 0.161
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CRC, Colorectal cancer; ESC, esophageal cancer; NPC, nasopharyngeal carcinoma; HB, Hospital-based

Association between IL-27 polymorphisms and cancer risk

The frequency distribution of genotype and allele of the IL-27 polymorphisms in cases and controls are indicated in Table 1, Table 2 and Table 3. Table 4 shows the main findings of our meta-analysis. Regarding rs153109 A>G variant, 21 independent studies were pooled and a random effect was applied due to the presence of significant heterogeneity. The finding revealed that rs153109 variant significantly increased the risk of cancer in heterozygous (OR=1.26, 95%CI=1.06-1.49, P=0.007, AG vs AA), homozygous (OR=1.18, 95%CI=1.01-1.37, p=0.33, GG vs AA), dominant (OR=1.25, 95%CI=1.07-1.47, P=0.006, AG+GG vs AA), and allele (OR=1.15, 95%CI=1.04-1.27, P=0.008, G vs A) genetic models (Figure 1 and Table 4).

Table 4.

The Pooled ORs and 95%CIs for the Association between IL-27 Polymorphisms and Cancer Susceptibility

Polymorphism Genetic models Test of association Test of heterogeneity Egger’s test Begg’s test
OR (95%CI) Z P χ2 I2 (%) P P-value P-value
rs153109 A>G AG vs AA 1.26 (1.06-1.49) 2.68 0.007 94 80 <0.00001 0.364 0.436
GG vs AA 1.18 (1.01-1.37) 2.13 0.033 33.44 43 0.021 0.835 0.679
AG+GG vs AA 1.25 (1.07-1.47) 2.73 0.006 97.52 80 <0.00001 0.282 0.243
GG vs AG+AA 1.05(0.93-1.19) 0.79 0.43 29.07 31 0.086 0.226 0.629
G vs A 1.15 (1.04-1.27) 2.54 0.01 73.78 74 <0.0001 0.259 0.364
rs17855750 T>G TG vs TT 1.11 (0.88-1.39) 0.89 0.38 53.06 75 <0.00001 0.962 0.87
G vs T 1.13 (0.89-1.44) 1.03 0.3 81.14 84 <0.00001 0.332 0.298
rs181206 T>C CT vs TT 1.05 (0.90-1.22) 0.62 0.53 5.73 0 0.45 0.892 0.453
C vs T 1.00 (0.81-1.23) 0.02 0.99 14.07 57 0.03 0.125 0.453
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Figure 1.

Figure 1

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The Flow Diagram of Screening and Study Selection for Meta-Analysis

Stratified analysis by cancer type (Table 5) revealed that rs153109 significantly increased the risk of gastrointestinal (GI) cancer in homozygous (OR=1.35, 95%CI=1.11-1.65, p=0.003), dominant (OR=1.28, 95%CI=1.02-1.59, p=0.030) and allele (OR=1.18, 95%CI=1.07-1.30, p=0.007) genetic models. Besides, the variant was significantly associated with colorectal cancer (CRC) and breast cancer susceptibility in all genetic model tested (Table 5).

Table 5.

Stratified Analysis of IL-17 Polymorphisms and Cancer Susceptibility

Type of cancer NO. AG vs AA GG vs AA AG+GG vs AA GG vs AG+AA G vs A
OR (95%CI) P OR (95%CI) P OR (95%CI) P OR (95%CI) P OR (95%CI) P
rs153109 A>G
GI cancer 5 1.25 (0.99-1.58) 0.6 1.35 (1.11-1.65) 0.003 1.28 (1.02-1.59) 0.03 1.19 (0.99-1.43) 0.06 1.18 (1.07-1.30) 0.007
Colorectal cancer 3 1.40 (1.17-1.67) 0.0003 1.45 (1.14-1.83) 0.002 1.41 (1.19-1.66) <0.0001 1.20 (0.97-1.49) 0.09 1.25 (1.12-1.41) 0.0001
Breast cancer 2 1.40 (1.02-1.91) 0.04 1.95 (1.27-3.01) 0.002 1.49 (1.05-2.10) 0.02 1.46 (1.10-2.46) 0.02 1.40 (1.07-1.81) 0.01
Esophageal cancer 2 1.20 (0.67-2.16) 0.55 0.81 (0.54-1.23) 0.32 0.86 (0.67-1.10) 0.23 0.88 (0.60-1.29) 0.51 0.90 (0.75-1.08) 0.24
rs17855750 T>G TG vs TT GG vs TT TG+GG vs TT GG vs TG+TT G vs T
GI cancer 4 1.07 (0.86-1.32) 0.54 _ _ _ _ _ _ 1.06 (0.83-1.35) 0.65
Colorectal cancer 2 1.18 (0.87-1.59) 0.29 _ _ _ _ _ _ 1.21 (0.92-1.59) 0.17
rs181206 T>C CT vs TT CC VS TT CT+CC VS TT CC VS CT+TT C VS T
Nasopharyngeal carcinoma 2 0.98 (0.70-1.37) 0.89 _ _ _ _ _ _ 0.98 (0.73-1.33) 0.91
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The findings showed that rs17855750 T>G, and rs181206 T>C variants were not associated with cancer risk (Table 4).

Heterogeneity and publication bias

Heterogeneity among studies involved in the meta-analysis is presented in Table 4. The findings indicated that heterogeneity exist among studies and random-effects was used to estimate the pooled OR and 95% CI (Figure 2 and Table 4).

Figure 2.

Figure 2

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The Forest Plot for Association between rs153109 A>G Polymorphism in the IL-27 and Cancer Susceptibility for G vs A

Begg’s funnel plot, Begg’s test, and Egger’s test (Figure 3, and Table 4) indicated no evidence of significant publication bias.

Figure 3.

Figure 3

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Begg’s Funnel Plot for Publication Bias Test for IL-27 rs153109 A>G Polymorphism and Cancer Risk for G vs A

Sensitivity analysis

After doing the sensitivity analyses, the pooled ORs showed no statistically significant changes in heterozygous, dominant, recessive, and allele representing that our findings are stable and reliable in overall analysis (Figure 4).

Figure 4.

Figure 4

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Sensitivity Analyses for Association between IL-27 rs153109 A>G Polymorphism and Cancer Risk for G vs A

Discussion

Several studies examined the association between IL-27 polymorphisms and the risk of various cancer (Wei et al., 2009; Zhao et al., 2009; Guo et al., 2012; Huang et al., 2012; Pan et al., 2012; Tao et al., 2012; Peng et al., 2013; Munretnam et al., 2014; Tang et al., 2014; Zhang et al., 2014a; Zhang et al., 2014b; Lyu et al., 2015; Pu et al., 2015; Zhang et al., 2015; Zhou et al., 2015; Ge and Xiao, 2016; Wang et al., 2016; Yu et al., 2016; Nie et al., 2017; Ghavami et al., 2018). The findings were controversial, though it is difficult to clarify the inconsistent findings. In this study, we conducted a comprehensive meta-analysis of all eligible studies to derive a more precise estimation of the relationship between IL-27 polymorphism and cancer risk. After pooling all the available data, the finding suggested that IL-27 rs153109 (-964 A>G) significantly increased the risk of overall cancer. Stratified analysis by cancer type designated that rs153109 polymorphism was positively associated with GI cancer, CRC and BC susceptibility. The findings did not support an association between rs17855750 (2905 T>G) and rs181206 (4730 T>C) polymorphisms and cancer susceptibility.

The molecular mechanisms by which variant increased the risk of cancer have not been clarified. It seems reasonable to speculate that rs153109 polymorphism effects on IL-27 expression. There is increasing evidence that the expression level of IL-27p28 gene is decreased in various cancers including epithelial ovarian cancer (Zhang et al., 2014b), bladder cancer (Zhou et al., 2015), esophageal cancer (Tao et al., 2012), osteosarcoma (Tang et al., 2014), as well as papillary thyroid cancer (Zhang et al., 2015). It has been shown that IL-27 differentially regulates the expression of several microRNAs (miR) such as hsa-miR-7702, hsa-miR-7704, hsa-miR-7704 hsa-miR-6852, and hsa-miR-6852 (Swaminathan et al., 2013; Poudyal et al., 2018).

Cytokines, secreted by cells of innate and adaptive immune systems, are small proteins that play key roles in immune responses. IL-27 is produced early after activation by antigen-presenting cells, including monocyte-derived dendritic cells and lipopolysaccharide-stimulated monocytes (Chiyo et al., 2004; Owaki et al., 2005). IL-27 mediates its biological functions via a heterodimeric receptor consisting of WSX-1 and glycoprotein 130 (gp130) (Pflanz et al., 2004). Binding of IL-27 to its receptor activates Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling (Kastelein et al., 2007). IL-27 has potent antitumor activity (Hisada et al., 2004; Chiyo et al., 2005). It exerts antitumor activity by promoting the generation of myeloid progenitor cells that can differentiate into M1 macrophages (Chiba et al., 2018). In addition, IL-27 synergizes with IL-12 to potentiate IFN-γ production by activated naive T-cell and natural killer-cell populations (Pflanz et al., 2002). Beside, IL-27 is a major stimulus of IL-10 production by T cell (Hunter and Kastelein, 2012; Liu et al., 2013).

Some limitations should be addressed in our meta-analysis. First, heterogeneity among studies was observed which may be result of difference of ethnicity, source of control, and cancer type. Second, this study focused on the impact of limited variants of IL-27 and cancer susceptibility. Gene-gene as well as gene-environment interactions could influence cancer risk. Third, all studies were from Asian populations; consequently, conclusions drawn may not apply to the all population. Finally, the sample sizes of the studies are relatively small particularly in subgroup analysis. So, the results should be interpreted with caution.

In conclusion, the findings of this meta-analysis provide evidence for an association between IL-27 rs153109 polymorphism and cancer risk. Well-designed studies with larger sample sizes in various cancer and different ethnicities are still needed in the future.

Acknowledgments

The authors like to acknowledge the Zahedan University of Medical Sciences research office to provide logistics for the literature search. The work was not supported by any operating grant and fund and was not a part of any graduate and under graduate thesis.

We would like to dedicate this article to Professor Mohamad Hashemi who passed away recently after the submission of this work. He was a pioneer in genetic studies.

Acknowledgments

We would like to dedicate this article to Professor Mohamad Hashemi who passed away recently after the submission of this work. He was a pioneer in genetic studies.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Chiba Y, Mizoguchi I, Furusawa J, et al. Interleukin-27 Exerts its antitumor effects by promoting differentiation of hematopoietic stem cells to M1 macrophages. Cancer Res. 2018;78:182–94. doi: 10.1158/0008-5472.CAN-17-0960. [DOI] [PubMed] [Google Scholar]
  2. Chiyo M, Shimozato O, Iizasa T, et al. Antitumor effects produced by transduction of dendritic cells-derived heterodimeric cytokine genes in murine colon carcinoma cells. Anticancer Res. 2004;24:3763–7. [PubMed] [Google Scholar]
  3. Chiyo M, Shimozato O, Yu L, et al. Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. Int J Cancer. 2005;115:437–42. doi: 10.1002/ijc.20848. [DOI] [PubMed] [Google Scholar]
  4. Devergne O, Hummel M, Koeppen H, et al. A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. J Virol. 1996;70:1143–53. doi: 10.1128/jvi.70.2.1143-1153.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Di Carlo E, Sorrentino C, Zorzoli A, et al. The antitumor potential of Interleukin-27 in prostate cancer. Oncotarget. 2014;5:10332–41. doi: 10.18632/oncotarget.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ge P, Xiao G. Interleukin-27 rs153109 polymorphism and the risk of non-small-cell lung cancer in a Chinese population. Onco Targets Ther. 2016;9:895–8. doi: 10.2147/OTT.S93226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ghavami A, Fathpour G, Amirghofran Z. Association of IL-27 rs153109 and rs17855750 polymorphisms with risk and response to therapy in acute lymphoblastic leukemia. Pathol Oncol Res. 2018;24:653–62. doi: 10.1007/s12253-017-0295-2. [DOI] [PubMed] [Google Scholar]
  8. Guo J, Qin A, Li R, et al. Association of interlenkin-27 gene polymorphism with genetic susceptibility to colorectal cancer. Chongqing Med. 2012;41:948–50. [Google Scholar]
  9. Hisada M, Kamiya S, Fujita K, et al. Potent antitumor activity of interleukin-27. Cancer Res. 2004;64:1152–6. doi: 10.1158/0008-5472.can-03-2084. [DOI] [PubMed] [Google Scholar]
  10. Huang ZQ, Wang JL, Pan GG, et al. Association of single nucleotide polymorphisms in IL-12 and IL-27 genes with colorectal cancer risk. Clin Biochem. 2012;45:54–9. doi: 10.1016/j.clinbiochem.2011.10.004. [DOI] [PubMed] [Google Scholar]
  11. Hunter CA, Kastelein R. Interleukin-27: balancing protective and pathological immunity. Immunity. 2012;37:960–9. doi: 10.1016/j.immuni.2012.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol. 2007;25:221–42. doi: 10.1146/annurev.immunol.22.012703.104758. [DOI] [PubMed] [Google Scholar]
  13. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343:78–85. doi: 10.1056/NEJM200007133430201. [DOI] [PubMed] [Google Scholar]
  14. Liu L, Wang S, Shan B, et al. IL-27-mediated activation of natural killer cells and inflammation produced antitumour effects for human oesophageal carcinoma cells. Scand J Immunol. 2008;68:22–9. doi: 10.1111/j.1365-3083.2008.02111.x. [DOI] [PubMed] [Google Scholar]
  15. Liu Z, Liu JQ, Talebian F, et al. IL-27 enhances the survival of tumor antigen-specific CD8+ T cells and programs them into IL-10-producing, memory precursor-like effector cells. Eur J Immunol. 2013;43:468–79. doi: 10.1002/eji.201242930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lyu S, Ye L, Wang O, et al. IL-27 rs153109 polymorphism increases the risk of colorectal cancer in Chinese Han population. Onco Targets Ther. 2015;8:1493–7. doi: 10.2147/OTT.S80255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Munretnam K, Alex L, Ramzi NH, et al. Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men. Mol Biol Rep. 2014;41:2501–8. doi: 10.1007/s11033-014-3107-8. [DOI] [PubMed] [Google Scholar]
  18. Nagai H, Oniki S, Fujiwara S, et al. Antitumor activities of interleukin-27 on melanoma. Endocr Metab Immune Disord Drug Targets. 2010;10:41–6. doi: 10.2174/187153010790827920. [DOI] [PubMed] [Google Scholar]
  19. Nie X, Yuan F, Chen P, et al. Association between IL-27 gene polymorphisms and risk of papillary thyroid carcinoma. Biomark Med. 2017;11:141–9. doi: 10.2217/bmm-2016-0283. [DOI] [PubMed] [Google Scholar]
  20. Owaki T, Asakawa M, Morishima N, et al. A role for IL-27 in early regulation of Th1 differentiation. J Immunol. 2005;175:2191–200. doi: 10.4049/jimmunol.175.4.2191. [DOI] [PubMed] [Google Scholar]
  21. Pan G, Lu D, Liao L, et al. Association of the genotype and serum level of IL-27 with nasopharyngeal carcinoma. Shandong Med J. 2012;52:18–20. [Google Scholar]
  22. Peng Q, Qin X, He Y, et al. Association of IL27 gene polymorphisms and HBV-related hepatocellular carcinoma risk in a Chinese population. Infect Genet Evol. 2013;16:1–4. doi: 10.1016/j.meegid.2013.01.015. [DOI] [PubMed] [Google Scholar]
  23. Pflanz S, Hibbert L, Mattson J, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol. 2004;172:2225–31. doi: 10.4049/jimmunol.172.4.2225. [DOI] [PubMed] [Google Scholar]
  24. Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002;16:779–90. doi: 10.1016/s1074-7613(02)00324-2. [DOI] [PubMed] [Google Scholar]
  25. Poudyal D, Herman A, Adelsberger JW, et al. A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression. Sci Rep. 2018;8:900. doi: 10.1038/s41598-018-19259-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pu Y, Chen P, Zhou B, et al. Association between polymorphisms in IL27 gene and renal cell carcinoma. Biomarkers. 2015;20:202–5. doi: 10.3109/1354750X.2015.1062555. [DOI] [PubMed] [Google Scholar]
  27. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. doi: 10.3322/caac.21254. [DOI] [PubMed] [Google Scholar]
  28. Swaminathan S, Hu X, Zheng X, et al. Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties. Biochem Biophys Res Commun. 2013;434:228–34. doi: 10.1016/j.bbrc.2013.03.046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tang YJ, Wang JL, Nong LG, et al. Associations of IL-27 polymorphisms and serum IL-27p28 levels with osteosarcoma risk. Medicine (Baltimore) 2014;93:e56. doi: 10.1097/MD.0000000000000056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tao YP, Wang WL, Li SY, et al. Associations between polymorphisms in IL-12A, IL-12B, IL-12Rbeta1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer. J Cancer Res Clin Oncol. 2012;138:1891–900. doi: 10.1007/s00432-012-1269-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang GQ, Zhao WH, Zhao XX, et al. Association between IL-27 2905T/G genotypes and the risk and survival of cervical cancer: a case-control study. Biomarkers. 2016;21:272–5. doi: 10.3109/1354750X.2015.1134665. [DOI] [PubMed] [Google Scholar]
  32. Wei YS, Lan Y, Luo B, et al. Association of variants in the interleukin-27 and interleukin-12 gene with nasopharyngeal carcinoma. Mol Carcinog. 2009;48:751–7. doi: 10.1002/mc.20522. [DOI] [PubMed] [Google Scholar]
  33. Yoshida H, Hunter CA. The immunobiology of interleukin-27. Annu Rev Immunol. 2015;33:417–43. doi: 10.1146/annurev-immunol-032414-112134. [DOI] [PubMed] [Google Scholar]
  34. Yoshimoto T, Chiba Y, Furusawa J, et al. Potential clinical application of interleukin-27 as an antitumor agent. Cancer Sci. 2015;106:1103–10. doi: 10.1111/cas.12731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yu XZ, Zhang Z, Zhou B, et al. Genetic polymorphisms of interleukin-27 is associated with endometrial cancer susceptibility in Chinese Han women. Int J Clin Exp Pathol. 2016;9:2718–25. [Google Scholar]
  36. Zhang S, Gao X, Wang Y, et al. Interleukin 27 -964A > G genetic polymorphism and serum IL-27p28 levels in Chinese patients with papillary thyroid cancer. Tumour Biol. 2015;36:8207–11. doi: 10.1007/s13277-015-3570-4. [DOI] [PubMed] [Google Scholar]
  37. Zhang S, Wang Y, Wang M, et al. IL-27 -964A>G polymorphism and the risk of breast cancer: a case-control study. Tumour Biol. 2014a;35:12099–102. doi: 10.1007/s13277-014-2512-x. [DOI] [PubMed] [Google Scholar]
  38. Zhang Z, Zhou B, Wu Y, et al. Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population. Immunogenetics. 2014b;66:85–92. doi: 10.1007/s00251-013-0753-2. [DOI] [PubMed] [Google Scholar]
  39. Zhao B, Meng LQ, Huang HN, et al. A novel functional polymorphism, 16974 A/C, in the interleukin-12-3’ untranslated region is associated with risk of glioma. DNA Cell Biol. 2009;28:335–41. doi: 10.1089/dna.2008.0845. [DOI] [PubMed] [Google Scholar]
  40. Zhou B, Zhang P, Tang T, et al. Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer. BMC Cancer. 2015;15:433. doi: 10.1186/s12885-015-1459-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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