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The il-17a g-197a and il-17F 7488T/c
polymorphisms are associated with increased
risk of cancer in asians: a meta-analysis
huifen Wang 1,*
Yanli Zhang 1,*
Zhaolan liu 2
Yin Zhang 3
hongchuan Zhao 1
shiyu Du 1
1
Department of gastroenterology,
china-Japan Friendship hospital,
2
center for evidence-Based chinese
Medicine, Beijing University of
chinese Medicine, 3institute of Basic
research in clinical Medicine, china
academy of chinese Medical sciences,
Beijing, People’s republic of china
*These authors contributed equally
to this work
Background: Interleukin-17 (IL-17) is a family of emerged pro-inflammatory cytokines. The
IL-17A and IL-17F are two important members of IL-17 family. Previous studies have shown
that the functional IL-17A G-197A and IL-17F 7488T/C polymorphisms may contribute to
susceptibility to cancer but the results were inconclusive. This meta-analysis was performed to
determine the exact association between IL-17 polymorphisms and cancer risk.
Methods: Online databases were searched to identify eligible case–control studies. Pooled odds
ratios (ORs) and confidence intervals (CIs) were calculated by fixed-effect models or randomeffect models. Publication bias was detected by Egger’s test and Begg’s test.
Results: Nine eligible case–control studies of IL-17A G-197A and seven studies of IL-17F
7488T/C, including 3,181 cases and 4,005 controls, were identified. Pooled analysis suggested
the variant IL-17A-197A allele was associated with increased risk cancer (GA/AA vs GG,
OR =1.27, 95% CI: 1.15, 1.41, Pheterogeneity =0.374; and A vs G, OR =1.30, 95% CI: 1.17, 1.45,
Pheterogeneity =0.021). For IL-17F 7488T/C, the homozygote 7488CC genotype significantly
increased risk of cancer (CC vs TC/TT, OR =1.36, 95% CI: 0.97, 1.91, Pheterogeneity =0.875; and
CC vs TT, OR =1.39, 95% CI: 1.03, 1.88, Pheterogeneity =0.979), especially for gastric cancer.
Conclusion: The variant IL-17A-197A allele and IL-17F 7488CC genotype were associated
with increased risk of cancer, especially for gastric cancer.
Keywords: interleukin-17, gene polymorphism, gastric cancer, risk, meta-analysis
Introduction
correspondence: shiyu Du
Department of gastroenterology, chinaJapan Friendship hospital, 2 Yinghua
Dongjie, chaoyang, Beijing 100029,
People’s republic of china
Tel +86 10 8420 5504
Fax +86 10 8420 5504
email dushiyu1975@126.com
Interleukin 17 (IL-17) family is a subset of newly identified pro-inflammatory cytokines.
The IL-17 family consists of six members, namely IL-17A, IL-17B, IL-17C, IL-17D,
IL-17D, and IL-17F, according to structure similarity and order of discovery.1,2 The
IL-17 receptor family includes five members: IL-17RA, IL-17RB, IL-17RC, IL-17RD,
and IL-17RE.1 IL-17A and IL-17F are produced by T helper 17 (Th17) cells3 and are
located just adjacent to each other on chromosome 6. Compared with other family
members, IL-17A and IL-17F are most homologous in amino acid sequence.4 IL-17A
is the fundamental member of IL-17 family. Evidence demonstrated that IL-17A could
induce the expression of various pro-inflammatory genes like metalloproteinase,5 by
activating pro-inflammatory signaling pathways. The IL-17A exerts its modulator
function in both innate and adaptive immune systems, and plays an important role in
the host defense against extracellular bacteria, protozoa, and fungi.6,7
Two common single nucleotide polymorphisms in the region of IL-17A (rs2275913,
G-197A) and IL-17F (rs763780, 7488T/C) have been identified and recent studies
suggest that the two functional single nucleotide polymorphisms influence the susceptibility to asthma,8 arthritis,9 and even cancer.10–12 But, the reports about IL-17A/F
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Wang et al
polymorphisms and cancer risk were controversial. Wang
et al11 found IL-17A G-197A, but not IL-17F 7488T/C,
polymorphism was not associated with the risk of breast
cancer. On the other hand, Zhou et al12 reported both IL-17A
G-197A and IL-17F 7488T/C polymorphisms were associated with the development and tumor stage of bladder cancer.
It remains inconclusive whether the IL-17A G-197A and
IL-17F 7488T/C polymorphisms are correlated with cancer
risk or not. Therefore, we performed this meta-analysis
to determine the strength of association between IL-17A
G-197A and IL-17F 7488T/C polymorphisms and cancer
risk by identifying and pooling eligible studies and evaluate
the effect of cancer types.
Materials and methods
selection of eligible studies
To identify eligible studies, we searched PubMed, EMBASE,
and Web of Science. Combination of the following key words
were used: “IL17A” OR “IL17F”, “rs275913” OR “rs763780”
to “IL-17” OR “interleukin 17”, “polymorphism” OR “single
nucleotide polymorphism” OR “SNP”, and “neoplasms”
OR “cancer” OR “tumor” for Asians. No limitation was
performed. The latest research was performed on April 13,
2015. Searching strategy is presented in the supplementary
materials (Table S1).
inclusion and exclusion criteria
Eligible studies were selected according to the following
inclusion criteria: 1) case–control studies; 2) investigating
the association between IL-17 polymorphisms (IL-17A
G-197A and IL-17F 7488T/C) and risk of cancer; 3) cancer
diagnosed by histopathology; and 4) available genotype
frequencies. Studies that did not provide a detailed genotype
frequency were excluded. Titles and abstracts of records were
first screened and full text papers were further evaluated to
confirm eligibility. Two reviewers (HW and HZ) extracted
eligible studies independently according to the inclusion criteria. Disagreement between the two reviewers was discussed
until consensus was achieved.
Data extraction
The following data were collected by two reviewers (HW
and HZ) independently with a predesigned data-collection
form: name of first author, year of publication, country where
the study was performed, cancer types, study design, number of cases and controls, genotype frequency in cases and
controls. According to the source of control, study design
was defined as hospital-based or population-based. Though
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we defined the hospital-based and hospital-based study, the
inclusion criteria and results were same. Sample size was
judged with a threshold of 500 participants (large .500 or
small ,500). Chi-square test for goodness was used for the
test of fit Hardy–Winberg equilibrium (HWE) in the controls
and P,0.05 was considered as disequilibrium of HWE. Two
reviewers reached consensus on each item.
statistical analysis
Pooled odds ratios (ORs) with 95% confidence intervals
(95% CIs) were calculated to estimate the association
strength between IL-17A G-197A and IL-17F 7488T/C
polymorphisms and cancer risk. Chi-square based on Q test
was used to check the statistical heterogeneity between studies, and the heterogeneity was considered significant when
P,0.10. The fixed-effects model (based on the Mantel–
Haenszel method) and random-effects model (based on the
DerSimonian–Laird method) were used to pool the data
from different studies. The fixed-effects model was used
when there was no significant heterogeneity; otherwise, the
random-effects model was applied.13 The pooled ORs were
achieved by calculating a weighted average of OR from
each study. A 95% CI was used for statistical significance
test and a 95% CI without 1 for OR indicating a significantly
increased or reduced cancer risk. The pooled ORs were
calculated for five comparison models: allele comparison
(A vs a), homozygote comparison (AA vs aa), heterozygote
comparison (Aa vs aa), dominant comparison (AA/Aa vs aa),
and recessive comparison (AA vs Aa/aa) (A: the mutant
allele, a: the wild allele; the -197A and 7488C alleles were
considered as mutant alleles).
Subgroup analyses were conducted according to cancer types, study design, HWE, and sample size. Subgroup
analysis was not performed for those subgroups with less
than two studies. Meta-regression was performed to detect
the source of heterogeneity. Publication bias was detected
by Begg’s test and the Egger’ linear regression test, and a
P,0.05 was considered significant.14 Sensitivity analyses
were performed to identify individual study’s effect on
pooled results and test the reliability of results; all P-values
were two-sided. All statistical analyses were calculated
with STATA software (version 12.0; StataCorp, College
Station, TX, USA).
Results
The process of study selection is shown in Figure 1. In summary, nine studies10–12,15–20 about IL-17A G-197A and seven
studies of IL-17F 7488T/C were identified. The baseline
Drug Design, Development and Therapy 2015:9
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il-17 polymorphisms associated with cancer risk
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Figure 1 Flowchart of study selection.
characteristics of eligible studies are shown in Table 1. Of
note, all eligible studies were conducted in Asia.
Meta-analysis results
A total of nine studies, involving 3,181 cases and 4,005
controls, were available for the analysis of IL-17A G-197A.
By pooling eligible studies, we found carriers of the
variant -197A allele were associated with a significantly
increased risk of cancer (GA/AA vs GG, OR =1.27, 95% CI:
1.15, 1.41; Pheterogeneity =0.374, Figure 2). Subgroup analyses
were further conducted to evaluate the influence of predefined
factors. The pooled results did not differ between different
cancer types, but significant associations were most found
in subgroups of population-based, large-sized studies and
studies in agreement with HWE. Meta-analysis for IL-17A
G-197A is shown in Table 2.
A total of seven studies, including 2,262 cases and 3,261
controls, contributed to the analysis of IL-17F 7488T/C.
Results showed that the homozygote of 7488CC genotype
significantly increased susceptibility to cancer (CC vs TC/TT,
Drug Design, Development and Therapy 2015:9
OR =1.36, 95% CI: 0.97, 1.91, Pheterogeneity =0.875; Figure 3).
Subgroup analysis indicated the IL-17F 7488T/C was only
associated with risk of gastric cancer but not other cancer
types. HWE results affected the pooled results, but study
design did not. Meta-analysis for IL-17F 7488T/C is shown
in Table 3.
Meta-regression analysis
As shown in Tables 2 and 3, significant heterogeneity was
observed in several comparison models, and meta-regression
analysis was performed. According to meta-regression
results, sample size, cancer types, and HWE were the source
of heterogeneity for both IL-17A G-197A and IL-17F
7488T/C.
Publication bias and sensitivity analysis
Egger’s test and Begg’s test were performed to detect
potential publication bias. The results suggested that no
publication bias existed for the analysis IL-17A G-197A
(Pbegg =0.466, Pegger =0.975; Figure 4A) nor the analysis of
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5161
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4
36
7
5
na
2
30
5
na
100
214
99
126
na
34
53
124
na
419
527
396
332
na
2
429
317
na
Yes
no
Yes
Yes
na
no
no
Yes
na
CC
TC
TT
4
55
6
4
na
13
21
4
na
CC
TT
Discussion
55
332
103
85
na
69
30
57
na
GG
GG
TC
Cases
49
204
58
80
72
12
67
78
21
2009
2010
2012
2012
2012
2012
2014
2013
2013
shibata17
Wu20
Wang11
Quan18
arisawa16
Yuan10
Zhang19
Zhou12
Raiei15
Notes: Yes means analyzed with the statistical software hWe. no means not analyzed with the statistical software hWe.
Abbreviations: hB, hospital-based studies; PB, population-based studies; il, interleukin; hWe, hardy–Winberg equilibrium; na, no data.
GA
299
371
245
215
293
24
187
204
72
175
193
198
168
218
2
258
164
78
69
250
92
76
84
20
48
68
44
AA
GA
124
485
234
142
137
60
102
154
61
94
210
165
93
112
12
110
79
56
gastric cancer
gastric cancer
Breast cancer
cervical cancer
gastric cancer
Ovarian cancer
gastric cancer
Bladder cancer
gastric cancer
hB
PB
PB
PB
hB
hB
PB
PB
PB
Japan
People’s republic of china
People’s republic of china
People’s republic of china
Japan
People’s republic of china
People’s republic of china
People’s republic of china
iran
AA
not
Yes
Yes
Yes
Yes
not
not
Yes
Yes
HWE
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IL-17F 7488T/C (Pbegg =0.133, Pegger =0.428; Figure 4B).
Individual studies’ influence was determined by sensitivity
analysis, which showed that the pooled results were stable
and not affected by individual studies (Figures S1 and S2).
221
540
382
222
na
10
209
240
na
IL-17F 7488T/C
Controls
IL-17A G-197A
Cases
Cancer types
Study
design
Country
Control
Year
Reference
Table 1 Baseline characteristics of eligible studies
5162
hB
PB
PB
PB
hB
hB
PB
PB
PB
Controls
HWE
Wang et al
Accumulating evidence indicates that IL-17 functions as
modulator in the process of tumorigenesis and metastasis.
It was found that IL-17 could induce and activate the STAT
signaling pathway and promote invasion of lung cancer.21
On the other hand, IL-17 also promotes tumor invasion
by modulating tumor microenvironment.22,23 Additionally,
Droeser et al found that IL-17 was associated with sensitivity to platinum-chemotherapy in ovarian carcinoma.24 As a
result, the expression level of IL-17 is unregulated in multiple
cancers, and the level of IL-17 is correlated with progression
and survival in glioblastoma and ovarian carcinoma,25,26 indicating the prognostic value of IL-17. The IL-17F 7488T/C
polymorphism causes an amino acid substitution from histamine to argentine at codon 161 (H161R), which leads to a
natural antagonist of wide-type IL-17. It was demonstrated
by Kawaguchi et al that this functional polymorphism could
influence the susceptibility to asthma.8 As for the IL-17A
G-197A polymorphism, which is located in the promoter
region of IL-17, it has been reported that, upon stimulation
peripheral blood mononuclear cells with variant genotypes
(-197AG or -197AA) secreted significantly more IL-17 than
the wild type (-197GG) cells.27 This study showed that the
IL-17A G-197A polymorphism could alter the promoter
activity of IL-17A and cause differential production of IL-17.
Taken together, these lines of evidence indicate the two polymorphisms can alter the function and production of IL-17
and it is biologically plausible that these two polymorphisms
may influence susceptibility to cancer.
In the current meta-analysis, we found that both IL-17A
G-197A and IL-17 7488T/C polymorphisms are associated
with increased of risk of cancer. For, the IL-17A G-197A
polymorphism, a significantly increased risk of cancer was
found in all comparisons. While for the IL-17F 7488T/C, only
carriers of the homozygote IL-17F 7488CC genotype were
associated significantly increased risk of cancer and individuals
with only one 7488C allele (the 7488CT genotype) showed
no change cancer risk in overall analysis. One of the possible
explanations is that the 7488C is a recessive allele, and in the
presence of 7488T allele, the antagonizing effect of the mutated
IL-17 will be compensated by the wild-type IL-17.
Subgroup analyses were performed to evaluate the effect
of cancer type, study design, sample size, and HWE. In the
Drug Design, Development and Therapy 2015:9
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il-17 polymorphisms associated with cancer risk
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Figure 2 Forest plot of il-17a g-197a polymorphism and cancer risk (ga/aa vs gg).
Abbreviations: IL, interleukin; OR, odds ratio; CI, conidence interval.
Table 2 Meta-analysis results for il-17a g-197a polymorphism
Studies
AA vs GG
OR (95% CI)
Het
OR (95% CI)
Het
OR (95% CI)
Het
OR (95% CI)
Het
OR (95% CI)
Het
Total
9
1.80
(1.40, 2.31)*
0.004
1.12
(1.01, 1.25)*
0.105
1.27
(1.15, 1.41)*
0.374
1.64
(1.22, 2.20)*
,0.001
1.30
(1.17, 1.45)*
0.021
source
of controls
PB
6
1.69
(1.32, 2.16)*
1.90
(1.01, 3.57)*
0.045
1.24
(1.10, 1.41)*
0.83
(0.66, 1.03)
0.802
1.34
(1.19, 1.51)*
1.08
(0.88, 1.33)
0.635
1.50
(1.15, 1.94)*
1.85
(0.94, 3.62)
0.006
1.30
(1.15, 1.48)*
1.24
(0.95, 1.62)
0.039
hB
3
cancer
types
gc
5
Others
4
hWe
Yes
6
no
3
sample
size
large
7
small
2
1.94
(1.32, 2.85)*
1.69
(1.23, 2.33)*
1.80
(1.37, 2.36)*
1.60
(0.80, 3.24)
1.78
(1.41, 2.25)*
1.03
(0.10, 10.27)
GA vs GG
0.037
0.001
0.175
0.02
0.01
0.019
0.009
1.06
(0.92, 1.21)
1.24
(1.04, 1.48)*
1.18
(1.03, 1.34)*
0.93
(0.58, 1.49)
1.13
(0.96, 1.32)
0.93
(0.39, 2.20)
GA/AA vs GG
0.527
0.131
0.257
0.057
0.356
0.071
0.213
1.21
(1.07, 1.38)*
1.36
(1.15, 1.61)*
1.303
(1.16, 1.47)*
1.17
(0.94, 1.44)
1.26
(1.14, 1.40)*
1.36
(0.90, 2.06)
AA vs GG/GA
0.319
0.517
0.247
0.557
0.137
0.508
0.077
1.93
(1.18, 3.15)*
1.42
(1.07, 1.89)*
1.64
(1.20, 2.26)*
1.52
(0.70, 3.28)
1.68
(1.24, 2.28)*
1.32
(0.30, 5.69)
A vs G
0.003
,0.001
0.139
,0.001
0.001
,0.001
0.004
1.33
(1.13, 1.56)*
1.27
(1.09, 1.49)*
1.32
(1.16, 1.49)*
1.22
(0.93, 1.59)
1.29
(1.18, 1.41)*
1.13
(0.46, 2.74)
0.055
0.013
0.15
0.027
0.068
0.132
0.005
Note: *Statistically signiicant association.
Abbreviations: het, P-value of heterogeneity; HB, hospital-based studies; PB, population-based studies; GC, gastric cancer; OR, odds ratio; CI, conidence interval;
hWe, hardy–Winberg equilibrium.
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Wang et al
Study ID
OR (95% CI)
% weight
Shibata et al17
1.88 (0.47, 7.58)
3.65
1.30 (0.84, 2.00)
48.88
Wang et al11
0.87 (0.29, 2.62)
9.07
18
1.19 (0.32, 4.48)
5.26
Yuan et al10
2.96 (0.64, 13.82)
3.22
Zhang et al19
1.41 (0.79, 2.52)
24.64
1.19 (0.32, 4.46)
5.27
1.35 (1.00, 1.82)
100.00
20
Wu et al
Quan et al
Zhou et al
12
Overall (l2=0.0%, P=0.925)
1
0.05
20
Figure 3 Forest plot of il-17F 7488T/c polymorphism and cancer risk (cc vs Tc/TT).
Abbreviations: IL, interleukin; OR, odds ratio, CI, conidence interval.
sub-group analysis of cancer types, we found the IL-17F polymorphism increased risk of gastric cancer but no significant
association was found for other cancers, indicating IL-17F
may have a cancer-type-specific function. Additionally, it
was also proposed that IL-17 production was associated with
helicobacter pylori infection (IL-8 and IL-ref24) and IL-17
polymorphism could affect gastric cancer susceptibility by
overproduction of IL-17 and subsequently overstimulation
of immune system.
Heterogeneity was observed in some comparison models.
We then performed a meta-regression analysis to identify the
source of the heterogeneity and found that cancer types, study
design, sample size, and HWE contributed to heterogeneity.
But Begg’s test and Egger’s test showed that the pooled
results were not biased. Sensitivity analysis also indicated
that the results were stable and robust.
Actually, no previous meta-analysis about IL-17A
and IL-17F has been performed. Our study made some
significant contributions to new knowledge for the IL17
single nucleotide polymorphisms researches.15,17,18,20 Our
study first reported that the variant IL-17A -197A allele and
IL-17F 7488CC genotype were associated with increased
risk of cancer, especially for gastric cancer. As genomewide association studies is a powerful tool to determine the
association between gene polymorphisms and cancer risk; we
have searched the databases and no genome-wide association
studies reported significant association between IL-17A or
IL-17F polymorphism and cancer risk. Limitations of this
Table 3 Meta-analysis results for il-17F 7488T/c polymorphism
Number CC vs TT
of Studies OR (95% CI)
Total
cancer
types
gc
Others
hWe
Yes
no
source of
controls
PB
hB
TC vs TT
Het OR (95% CI)
TC/CC vs TT
Het OR (95% CI)
Het
CC vs TT/TC
C vs T
OR (95% CI)
Het OR (95% CI)
Het
7
1.39 (1.03, 1.88)* 0.979 1.02 (0.78, 1.33) 0.001 1.05 (0.82, 1.35) 0.001
1.35 (1.00, 1.82)* 0.925 1.08 (0.90, 1.30) 0.009
3
4
1.49 (1.06, 2.10)* 0.937 1.29 (1.00, 1.65)* 0.18 1.33 (1.09, 1.64)* 0.24
1.04 (0.53, 2.05) 0.983 0.85 (0.61, 1.19) 0.059 0.87 (0.64, 1.18) 0.081
1.36 (0.97, 1.91) 0.875 1.32 (1.15, 1.51)* 0.466
1.32 (0.70, 2.46) 0.65 0.93 (0.75, 1.15) 0.174
4
3
1.15 (0.61, 2.17) 0.868 0.92 (0.71, 1.19) 0.071 0.93 (0.73, 1.19) 0.08
1.47 (1.04, 2.07)* 0.989 1.29 (0.89, 1.88) 0.176 1.38 (1.06, 1.79)* 0.254
1.18 (0.62, 2.21) 0.87 0.95 (0.77, 1.17) 0.133
1.41 (1.00, 1.97)* 0.598 1.34 (1.17, 1.55)* 0.635
5
2
1.37 (1.00, 1.87)* 0.917 1.04 (0.76, 1.43) 0.001 1.06 (0.79, 1.44) ,0.001 1.27 (0.93, 1.74) 0.963 1.09 (0.83, 1.45) 0.923
1.69 (0.52, 5.42) 0.771 0.90 (0.46, 1.77) 0.251 1.00 (0.61, 1.61) 0.295 2.39 (0.86, 6.64) 0.664 1.07 (0.84, 1.37) 0.002
Note: *Signiicant association.
Abbreviations: OR, odds ratio; CI, conidence interval; Het, P-value of heterogeneity; hB, hospital-based studies; PB, population-based studies; gc, gastric cancer; hWe,
hardy–Winberg equilibrium.
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Drug Design, Development and Therapy 2015:9
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il-17 polymorphisms associated with cancer risk
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Figure 4 Funnel plots of il-17a g-197a (A) and il-17F 7488T/c (B) polymorphisms.
Abbreviations: il, interleukin; Or, odds ratio.
meta-analysis should be noted. First, number of eligible
studies was relatively small. Given limited number of studies,
subgroup analyses for common cancer types was unavailable.
In this meta-analysis, only subgroup analysis for gastric cancer was performed. Second, due to lack of individual data,
we could not analyze the effect of other confounding factors,
like smoking status, living habits, and so on.
Conclusion
In this meta-analysis, we pooled 3,181 cases and 4,005
controls and found that carriers of the variant IL-17A-197A
allele and IL-17F 7488CC genotype were associated with
increased risk of cancer, especially for gastric cancer.
Acknowledgments
This study was granted by China-Japan Friendship Hospital
Youth Science and Technology Excellence Project (No. 2015QNYC-B-02) and the Research Fund of the China-Japan
Friendship Hospital (No. 2014-2-MS-9).
Disclosure
The authors report no conflicts of interest in this work.
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il-17 polymorphisms associated with cancer risk
Supplementary materials
Table S1 searching strategy
searching strategy for PubMed: ((interleukin-17) Or il17) anD (((single nucleotide polymorphism) Or polymorphism) Or snP) anD (((neoplasms)
OR cancer) OR tumor); records identiied: 32
searching strategy for PubMed: ((interleukin-17) Or il17) anD (((single nucleotide polymorphism) Or polymorphism) Or snP) anD (((neoplasms)
OR cancer) OR tumor); records identiied: 10
Searching strategy for Web of Science: (interleukin-17) AND (polymorphism) AND (cancer); records identiied from Web of Science: 21
searching strategy for china national Knowledge infrastructure: ((interleukin-17) Or il17) anD (polymorphism) Or mutation) anD (tumor) Or
cancer) records identiied: 27
0HWDDQDO\VLVHVWLPDWHVJLYHQQDPHGVWXG\LVRPLWWHG
/RZHU&,OLPLW
(VWLPDWH
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6KLEDWDHWDO
:XHWDO
:DQJHWDO
4XDQHWDO
$ULVDZDHWDO
<XDQHWDO
=KDQJHWDO
=KRXHWDO
5DILHLHWDO
2GGVUDWLR
Figure S1 sensitivity analysis of il-17a g-197a polymorphism.
Abbreviations: IL, interleukin, CI, conidence interval.
Drug Design, Development and Therapy 2015:9
submit your manuscript | www.dovepress.com
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5167
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Wang et al
0HWDDQDO\VLVHVWLPDWHVJLYHQQDPHGVWXG\LVRPLWWHG
/RZHU&,OLPLW
6KLEDWDHWDO
(VWLPDWH
8SSHU&,OLPLW
:XHWDO
:DQJHWDO
4XDQHWDO
<XDQHWDO
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=KRXHWDO
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Figure S2 sensitivity analysis of il-17F 7488T/c polymorphism.
Abbreviations: IL, interleukin, CI, conidence interval.
References
1. Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of
interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol.
2009;70:547–551.
2. Wu X, Zeng Z, Chen B, et al. Association between polymorphisms in
interleukin-17A and interleukin-17F genes and risks of gastric cancer.
Int J Cancer. 2010;127:86–92.
3. Wang L, Jiang Y, Zhang Y, et al. Association analysis of IL-17A and
IL-17F polymorphisms in Chinese Han women with breast cancer. PLoS
One. 2012;7:e34400.
4. Quan Y, Zhou B, Wang Y, et al. Association between IL17 polymorphisms
and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;
2012:258293.
5. Arisawa T, Tahara T, Shiroeda H, et al. Genetic polymorphisms of IL17A
and pri-microRNA-938, targeting IL17A 3′-UTR, influence susceptibility
to gastric cancer. Hum Immunol. 2012;73:747–752.
6. Yuan Y, Hu Y, Tao K, RZ. Association analysis of IL-17A and IL-17F
gene polymorphism with epithelial ovarian cancer. J Hunan Normal
Univ. 2012;9:21–24.
7. Zhang X, Zheng L, Sun Y. Analysis of the association of interleukin-17
gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population. Tumour Biol. 2014;35:
1575–1580.
8. Zhou B, Zhang P, Wang Y, et al. Interleukin-17 gene polymorphisms
are associated with bladder cancer in a Chinese Han population. Mol
Carcinog. 2013;52:871–878.
9. Rafiei A, Hosseini V, Janbabai G, et al. Polymorphism in the interleukin17A promoter contributes to gastric cancer. World J Gastroenterol.
2013;19:5693–5699.
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