Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Sources and Literature Search
2.2. Eligibility Criteria and Study Selection
2.3. Data Extraction
2.4. Quality Assessment
2.5. Statistical Analysis
3. Results
3.1. Study Selection
3.2. Full Text Evaluation
3.3. Study Characteristics
3.4. Meta-Analysis
3.5. Subgroup Analysis
3.6. Meta-Regression
3.7. Sensitivity Analysis
3.8. Publication Bias
3.9. Trial Sequential Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CI | Confidence interval |
FRET | Fluorescence resonance energy transfer. |
HWE | Hardy–Weinberg equilibrium |
HRM | High resolution melt |
IL | Interleukin |
IARC | International Agency for Research on Cancer |
OR | Odds ratio |
OC | Oral cancer |
PCR | Polymerase chain reaction |
RFLP | Restriction fragment length polymorphism; |
OSCC | Oral squamous cell carcinoma |
References
- Ghantous, Y.; Elnaaj, A. Global incidence and risk factors of oral cancer. Harefuah 2017, 156, 645–649. [Google Scholar]
- Warnakulasuriya, S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009, 45, 309–316. [Google Scholar] [CrossRef]
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ren, Z.H.; Hu, C.Y.; He, H.R.; Li, Y.J.; Lyu, J. Global and regional burdens of oral cancer from 1990 to 2017: Re-sults from the global burden of disease study. Cancer Commun. 2020, 40, 81–92. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bagan, J.; Sarrion, G.; Jimenez, Y. Oral cancer: Clinical features. Oral Oncol. 2010, 46, 414–417. [Google Scholar] [CrossRef] [PubMed]
- Gharat, S.A.; Momin, M.; Bhavsar, C. Oral squamous cell carcinoma: Current treatment strategies and nano-technology-based approaches for prevention and therapy. Crit. Rev. Ther. Drug Carr. Syst. 2016, 33, 363–400. [Google Scholar] [CrossRef]
- Neville, B.W.; Day, T.A. Oral cancer and precancerous lesions. CA Cancer J. Clin. 2002, 52, 195–215. [Google Scholar] [CrossRef] [PubMed]
- Anand, P.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Tharakan, S.T.; Lai, O.S.; Sung, B.; Aggarwal, B.B. Cancer is a Preventable Disease that Requires Major Lifestyle Changes. Pharm. Res. 2008, 25, 2200. [Google Scholar] [CrossRef] [Green Version]
- Rivera, C. Essentials of oral cancer. Int. J. Clin. Exp. Pathol. 2015, 8, 11884–11894. [Google Scholar]
- Boffetta, P.; Hecht, S.; Gray, N.; Gupta, P.; Straif, K. Smokeless tobacco and cancer. Lancet Oncol. 2008, 9, 667–675. [Google Scholar] [CrossRef]
- Madani, A.H.; Dikshit, M.; Bhaduri, D. Risk for oral cancer associated to smoking, smokeless and oral dip products. Indian J. Public Health 2012, 56, 57–60. [Google Scholar] [CrossRef]
- Auluck, A.; Hislop, G.; Poh, C.; Zhang, L.; Rosin, M.P. Areca nut and betel quid chewing among South Asian immigrants to Western countries and its implications for oral cancer screening. Rural. Remote Health 2009, 9, 1118. [Google Scholar]
- Chaturvedi, A.K.; Engels, E.A.; Pfeiffer, R.M.; Hernandez, B.Y.; Xiao, W.; Kim, E.; Jiang, B.; Goodman, M.T.; Sibug-Saber, M.; Cozen, W.; et al. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. J. Clin. Oncol. 2011, 29, 4294–4301. [Google Scholar] [CrossRef]
- Meurman, J.H. Infectious and dietary risk factors of oral cancer. Oral Oncol. 2010, 46, 411–413. [Google Scholar] [CrossRef] [PubMed]
- Groome, P.A.; Rohland, S.L.; Hall, S.F.; Irish, J.; Mackillop, W.J.; O’Sullivan, B. A population-based study of fac-tors associated with early versus late stage oral cavity cancer diagnoses. Oral Oncol. 2011, 47, 642–647. [Google Scholar] [CrossRef] [PubMed]
- Argiris, A.; Karamouzis, M.V.; Raben, D.; Ferris, R.L. Head and neck cancer. Lancet 2008, 371, 1695–1709. [Google Scholar] [CrossRef]
- Su, S.; Chien, M.; Lin, C.; Chen, M.; Yang, S. RAGE Gene Polymorphism and Environmental Factor in the Risk of Oral Cancer. J. Dent. Res. 2014, 94, 403–411. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Scully, C.; Field, J.; Tanzawa, H. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol. 2000, 36, 256–263. [Google Scholar] [CrossRef]
- Taniyama, Y.; Takeuchi, S.; Kuroda, Y. Genetic Polymorphisms and Oral Cancer. J. UOEH 2010, 32, 221–236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schiegnitz, E.; Kämmerer, P.W.; Schön, H.; Blatt, S.; Berres, M.; Sagheb, K.; Al-Nawas, B. Proinflammatory cyto-kines as serum biomarker in oral carcinoma—A prospective multi-biomarker approach. J. Oral Pathol. Med. 2018, 47, 268–274. [Google Scholar] [CrossRef] [PubMed]
- Watkins, L.R.; Wiertelak, E.P.; Goehler, L.E.; Smith, K.P.; Martin, D.; Maier, S.F. Characterization of cyto-kine-induced hyperalgesia. Brain Res. 1994, 654, 15–26. [Google Scholar] [CrossRef]
- Watkins, L.R.; Maier, S.F.; Goehler, L.E. Immune activation: The role of pro-inflammatory cytokines in inflamma-tion, illness responses and pathological pain states. Pain 1995, 63, 289–302. [Google Scholar] [CrossRef]
- Terry, C.F.; Loukaci, V.; Green, F.R. Cooperative influence of genetic polymorphisms on interleukin 6 transcrip-tional regulation. J. Biol. Chem. 2000, 275, 18138–18144. [Google Scholar] [CrossRef] [Green Version]
- Rezaei, F.; Mozaffari, H.R.; Tavasoli, J.; Zavattaro, E.; Imani, M.M.; Sadeghi, M. Evaluation of Serum and Salivary Interleukin-6 and Interleukin-8 Levels in Oral Squamous Cell Carcinoma Patients: Systematic Review and Meta-Analysis. J. Interf. Cytokine Res. 2019, 39, 727–739. [Google Scholar] [CrossRef]
- Wang, Z.; Wang, C.; Zhao, Z.; Liu, F.; Guan, X.; Lin, X.; Zhang, L. Association between -251A>T polymorphism in the interleukin-8 gene and oral cancer risk: A meta-analysis. Gene 2013, 522, 168–176. [Google Scholar] [CrossRef]
- Yang, L.; Zhu, X.; Liang, X.; Ling, Z.; Li, R. Association of IL-8-251A>T polymorphisms with oral cancer risk: Evidences from a meta-analysis. Tumor Biol. 2014, 35, 9211–9218. [Google Scholar] [CrossRef] [PubMed]
- Fernández-Mateos, J.; Seijas-Tamayo, R.; Klain, J.C.A.; Borgoñón, M.P.; Pérez-Ruiz, E.; Mesía, R.; Del Barco, E.; Coloma, C.S.; Dominguez, A.R.; Daroqui, J.C. Genetic susceptibility in head and neck squamous cell carcinoma in a Spanish population. Cancers 2019, 11, 493. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaur, P.; Mittal, M.; Mohanti, B.; Das, S.N. Functional variants of IL4 and IL6 genes and risk of tobacco-related oral carcinoma in high-risk Asian Indians. Oral Dis. 2011, 17, 720–726. [Google Scholar] [CrossRef]
- Rezaei, F.; Doulatparast, D.; Sadeghi, M. Common Polymorphisms of Interleukin-10 (-1082A/G, -592A/C, and -819C/T) in Oral Cancers: An Updated Meta-Analysis. J. Interf. Cytokine Res. 2020, 40, 357–369. [Google Scholar] [CrossRef] [PubMed]
- Singh, P.K.; Chandra, G.; Bogra, J.; Gupta, R.; Kumar, V.; Hussain, S.R.; Jain, A.; Mahdi, A.A.; Ahmad, M.K. As-sociation of genetic polymorphism in the interleukin-8 gene with risk of oral cancer and its correlation with pain. Biochem. Genet. 2016, 54, 95–106. [Google Scholar] [CrossRef] [PubMed]
- Vairaktaris, E.; Yapijakis, C.; Serefoglou, Z.; Avgoustidis, D.; Critselis, E.; Spyridonidou, S.; Vylliotis, A.; Derka, S.; Vassiliou, S.; Nkenke, E.; et al. Gene expression polymorphisms of interleukins-1β, -4, -6, -8, -10, and tumor necrosis factors-α, -β: Regression analysis of their effect upon oral squamous cell carcinoma. J. Cancer Res. Clin. Oncol. 2008, 134, 821–832. [Google Scholar] [CrossRef]
- Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [Green Version]
- Higgins, J.P. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.0. 1; The Cochrane Collaboration: London, UK, 2008; Available online: http://www.cochrane-handbook.org (accessed on 30 January 2012).
- Higgins, J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 2002, 21, 1539–1558. [Google Scholar] [CrossRef] [PubMed]
- Higgins, J.P.T.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ 2003, 327, 557–560. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- DerSimonian, R.; Laird, N. Meta-analysis in clinical trials. Control. Clin. Trials 1986, 7, 177–188. [Google Scholar] [CrossRef]
- Mantel, N.; Haenszel, W. Statistical Aspects of the Analysis of Data from Retrospective Studies of Disease. J. Natl. Cancer Inst. 1959, 22, 719–748. [Google Scholar] [CrossRef] [Green Version]
- Imberger, G.; Thorlund, K.; Gluud, C.; Wetterslev, J. False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: An empirical review. BMJ Open 2016, 6, e011890. [Google Scholar] [CrossRef]
- Wetterslev, J.; Jakobsen, J.C.; Gluud, C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med. Res. Methodol. 2017, 17, 1–18. [Google Scholar] [CrossRef] [Green Version]
- Campa, D.; Hashibe, M.; Zaridze, D.; Szeszenia-Dabrowska, N.; Mates, I.N.; Janout, V.; Holcatova, I.; Fabiánová, E.; Gaborieau, V.; Hung, R.J. Association of common polymorphisms in inflammatory genes with risk of devel-oping cancers of the upper aerodigestive tract. Cancer Causes Control 2007, 18, 449–455. [Google Scholar] [CrossRef]
- De Matos, F.R.; Santos, E.D.M.; Santos, H.B.D.P.; Machado, R.A.; Lemos, T.M.A.M.; Coletta, R.D.; Freitas, R.D.A. Association of polymorphisms in IL-8, MMP-1 and MMP-13 with the risk and prognosis of oral and oropharyngeal squamous cell carcinoma. Arch. Oral Biol. 2019, 108, 104547. [Google Scholar] [CrossRef]
- Hu, Y.; Liu, B.; Su, T.; Cheng, J.; Zhao, W.; Yang, H. IL-8–251 single nucleotide polymorphism in the recurrence of squamous cell carcinoma of tongue. J. Pract. Stomatol. 2012, 28, 328–332. [Google Scholar]
- Kietthubthew, S.; Wickliffe, J.; Sriplung, H.; Ishida, T.; Chonmaitree, T.; Au, W.W. Association of polymorphisms in proinflammatory cytokine genes with the development of oral cancer in Southern Thailand. Int. J. Hyg. Environ. Health 2010, 213, 146–152. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.M.; Yeh, C.J.; Yu, C.C.; Chou, M.Y.; Lin, C.H.; Wei, L.H.; Lin, C.W.; Yang, S.F.; Chien, M.H. Impact of inter-leukin-8 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan. Oral Dis. 2012, 18, 307–314. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, Y.; Kondo, S.; Shirai, A.; Furukawa, M.; Yoshizaki, T. A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer. Auris Nasus Larynx 2008, 35, 381–389. [Google Scholar] [CrossRef]
- Singh, P.K.; Chandra, G.; Bogra, J.; Gupta, R.; Kumar, V.; Jain, A.; Hussain, S.R.; Mahdi, A.A.; Ahmad, M.K. As-sociation of interleukin-6 genetic polymorphisms with risk of OSCC in Indian population. Meta Gene 2015, 4, 142–151. [Google Scholar] [CrossRef] [PubMed]
- Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, Inflammation, and Cancer. Cell 2010, 140, 883–899. [Google Scholar] [CrossRef] [Green Version]
- He, B.; Zhang, Y.; Pan, Y.; Xu, Y.; Gu, L.; Chen, L.; Wang, S. Interleukin 1 beta (IL1B) promoter polymorphism and cancer risk: Evidence from 47 published studies. Mutagenesis 2011, 26, 637–642. [Google Scholar] [CrossRef] [PubMed]
- Feller, L.; Altini, M.; Lemmer, J. Inflammation in the context of oral cancer. Oral Oncol. 2013, 49, 887–892. [Google Scholar] [CrossRef] [PubMed]
- Vairaktaris, E.; Yiannopoulos, A.; Vylliotis, A.; Yapijakis, C.; Derka, S.; Vassiliou, S.; Nkenke, E.; Serefoglou, Z.; Ragos, V.; Tsigris, C. Strong Association of Interleukin-6-174 G>C Promoter Polymorphism with Increased Risk of Oral Cancer; SAGE Publications: London, UK, 2006. [Google Scholar]
- Ugurel, S.; Rappl, G.; Tilgen, W.; Reinhold, U. Increased Serum Concentration of Angiogenic Factors in Malignant Melanoma Patients Correlates with Tumor Progression and Survival. J. Clin. Oncol. 2001, 19, 577–583. [Google Scholar] [CrossRef] [PubMed]
- Ren, Y.; Poon, R.T.-P.; Tsui, H.-T.; Chen, W.-H.; Li, Z.; Lau, C.; Yu, W.-C.; Fan, S.-T. Interleukin-8 serum levels in patients with hepatocellular carcinoma: Correlations with clinicopathological features and prognosis. Clin. Cancer Res. 2003, 9, 5996–6001. [Google Scholar]
- Kassim, S.K.; El-Salahy, E.M.; Fayed, S.T.; Helal, S.A.; Helal, T.; Azzam, E.E.-D.; Khalifa, A. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin. Biochem. 2004, 37, 363–369. [Google Scholar] [CrossRef] [PubMed]
- Benoy, I.H.; Salgado, R.; Van Dam, P.; Geboers, K.; Van Marck, E.; Scharpé, S.; Vermeulen, P.B.; Dirix, L.Y. In-creased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemina-tion and survival. Clin. Cancer Res. 2004, 10, 7157–7162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Review Author 2 (F.R.) | Review Author 1 (M.S.) | ||||
Include | Exclude | Unsure | Total | ||
Include | 9 | 0 | 0 | 9 | |
Exclude | 0 | 9 | 0 | 9 | |
Unsure | 2 | 0 | 0 | 2 | |
Total | 11 | 9 | 0 | 20 |
First Name, Publication Year | Country | Ethnicity | Source of Controls | Type of Cancer | Genotyping Method | Polymorphism |
---|---|---|---|---|---|---|
Campa, 2007 [40] | Central/Eastern Europe | Caucasian | Population-based | Oral SCC | TaqMan | IL-8 (-251T/A) |
Shimizu, 2008 [45] | Japan | Asian | Population-based | Tongue SCC | PCR-FRET | IL-8 (- 251T/A) |
Vairaktaris, 2008 [31] | Greece | Caucasian | Population-based | Oral SCC | PCR-RFLP | IL-8 (-251T/A) & IL-6 (-174G/C) |
Kietthubthew, 2010 [43] | Thailand | Asian | Population-based | Oral SCC | TaqMan | IL-8 (-251T/A) |
Gaur, 2011 [28] | India | Caucasian | Hospital-based | Oral SCC | PCR-RFLP | IL-6 (-174G/C) |
Hu, 2012 [42] | China | Asian | Hospital-based | Oral SCC | PCR-HRM | IL-8 (-251T/A) |
Liu, 2012 [44] | Taiwan | Asian | Population-based | Oral SCC | PCR-RFLP | IL-8 (-251T/A) |
Singh, 2015 [46] | India | Caucasian | Population-based | Oral SCC | PCR-RFLP | IL-6 (-174G/C) |
Singh, 2016 [30] | India | Caucasian | Population-based | Oral SCC | PCR-RFLP | IL-8 (-251T/A) |
de Matos, 2019 [41] | Brazil | Mixed | Population-based | Oral SCC | TaqMan | IL-8 (-251T/A) |
Fernández-Mateos, 2019 [27] | Spain | Caucasian | Hospital-based | Oral SCC | TaqMan | IL-6 (-174G/C) |
First Name, Publication Year | Polymorphism | Case | Control | p-Valueof HWE | Quality Score | ||||||||||
T | A | TT | TA | AA | MAF | T | A | TT | TA | AA | MAF | ||||
Campa, 2007 [40] | IL-8 (-251T/A) | 152 | 154 | 40 | 72 | 41 | 0.50 | 950 | 846 | 241 | 468 | 189 | 0.47 | 0.169 | 11 |
Shimizu, 2008 [45] | IL-8 (-251T/A) | 92 | 46 | 31 | 30 | 8 | 0.33 | 121 | 61 | 38 | 45 | 8 | 0.34 | 0.295 | 9 |
Vairaktaris, 2008 [31] | IL-8 (-251T/A) | 200 | 116 | 54 | 88 | 14 | 0.37 | 240 | 72 | 84 | 72 | 0 | 0.23 | <0.001 | 9 |
Kietthubthew, 2010 [43] | IL-8 (-251T/A) | 85 | 41 | 32 | 21 | 10 | 0.32 | 117 | 81 | 34 | 49 | 16 | 0.41 | 0.813 | 10 |
Hu, 2012 [42] | IL-8 (-251T/A) | 135 | 83 | 42 | 51 | 16 | 0.38 | 36 | 24 | 11 | 14 | 5 | 0.40 | 0.879 | 9 |
Liu, 2012 [44] | IL-8 (-251T/A) | 325 | 215 | 97 | 131 | 42 | 0.40 | 404 | 296 | 120 | 164 | 66 | 0.42 | 0.454 | 10 |
Singh, 2016 [30] | IL-8 (-251T/A) | 323 | 277 | 106 | 111 | 83 | 0.46 | 257 | 343 | 34 | 189 | 77 | 0.57 | <0.001 | 9 |
de Matos, 2019 [41] | IL-8 (-251T/A) | 135 | 115 | 34 | 67 | 24 | 0.46 | 135 | 125 | 37 | 61 | 32 | 0.48 | 0.492 | 9 |
First Name, Publication Year | Polymorphism | Case | Control | p-Value of HWE | Quality Score | ||||||||||
G | C | GG | GC | CC | MAF | G | C | GG | GC | CC | MAF | ||||
Vairaktaris, 2008 [31] | IL-6 (-174G/C) | 186 | 138 | 42 | 102 | 18 | 0.43 | 240 | 72 | 90 | 60 | 6 | 0.23 | 0.297 | 9 |
Gaur, 2011 [28] | IL-6 (-174G/C) | 231 | 49 | 98 | 35 | 7 | 0.18 | 171 | 69 | 65 | 41 | 14 | 0.29 | 0.069 | 8 |
Singh, 2015 [46] | IL-6 (-174G/C) | 401 | 143 | 150 | 101 | 21 | 0.26 | 305 | 65 | 129 | 47 | 9 | 0.18 | 0.094 | 10 |
Fernández-Mateos, 2019 [27] | IL-6 (-174G/C) | 57 | 83 | 12 | 33 | 25 | 0.59 | 39 | 101 | 8 | 23 | 39 | 0.72 | 0.126 | 11 |
Genetic Model | First Author, Publication Year | Case | Control | Weight | Odds Ratio | ||
---|---|---|---|---|---|---|---|
Events | Total | Events | Total | M-H, Random, 95%CI | |||
A vs. T | Campa, 2007 | 154 | 306 | 846 | 1795 | 14.7% | 1.14 [0.89, 1.45] |
Vairaktaris, 2008 | 116 | 316 | 72 | 312 | 12.8% | 1.93 [1.36, 2.74] | |
Shimizu, 2008 | 46 | 138 | 61 | 182 | 10.6% | 0.99 [0.62, 1.59] | |
Kietthubthew, 2010 | 41 | 126 | 81 | 198 | 10.6% | 0.70 [0.44, 1.11] | |
Hu, 2012 | 83 | 218 | 24 | 60 | 8.7% | 0.92 [0.51, 1.65] | |
Liu, 2012 | 215 | 540 | 296 | 700 | 15.0% | 0.90 [0.72, 1.13] | |
Singh, 2016 | 277 | 600 | 343 | 600 | 15.0% | 0.64 [0.51, 0.81] | |
de Matos, 2019 | 115 | 250 | 125 | 260 | 12.8% | 0.92 [0.65, 1.30] | |
Subtotal (95%CI) | 2494 | 4107 | 100.0% | 0.97 [0.76, 1.23] | |||
Total events | 1047 | 1848 | |||||
Heterogeneity: Tau² = 0.09; Chi² = 31.24, df = 7 (p < 0.0001); I² = 78% | Test for overall effect: Z = 0.28 (p = 0.78) | ||||||
AA vs. TT | Campa, 2007 | 41 | 81 | 189 | 430 | 17.2% | 1.31 [0.81, 2.10] |
Shimizu, 2008 | 8 | 39 | 8 | 46 | 10.3% | 1.23 [0.41, 3.64] | |
Vairaktaris, 2008 | 14 | 68 | 0 | 84 | 2.6% | 44.96 [2.63, 769.34] | |
Kietthubthew, 2010 | 10 | 42 | 16 | 50 | 11.9% | 0.66 [0.26, 1.68] | |
Hu, 2012 | 16 | 58 | 5 | 16 | 9.2% | 0.84 [0.25, 2.79] | |
Liu, 2012 | 42 | 139 | 66 | 186 | 17.3% | 0.79 [0.49, 1.26] | |
Singh, 2016 | 83 | 189 | 77 | 111 | 17.0% | 0.35 [0.21, 0.57] | |
de Matos, 2019 | 24 | 58 | 32 | 69 | 14.5% | 0.82 [0.40, 1.65] | |
Subtotal (95%CI) | 674 | 992 | 100.0% | 0.86 [0.53, 1.41] | |||
Total events | 238 | 393 | |||||
Heterogeneity: Tau² = 0.31; Chi² = 24.02, df = 7 (p = 0.001); I² = 71% | Test for overall effect: Z = 0.59 (p = 0.55) | ||||||
TA vs. TT | Campa, 2007 | 72 | 112 | 468 | 709 | 13.4% | 0.93 [0.61, 1.41] |
Shimizu, 2008 | 30 | 61 | 45 | 83 | 11.9% | 0.82 [0.42, 1.58] | |
Vairaktaris, 2008 | 88 | 142 | 72 | 156 | 13.2% | 1.90 [1.20, 3.02] | |
Kietthubthew, 2010 | 21 | 53 | 49 | 83 | 11.7% | 0.46 [0.23, 0.92] | |
Liu, 2012 | 131 | 228 | 164 | 284 | 13.7% | 0.99 [0.69, 1.41] | |
Hu, 2012 | 51 | 93 | 14 | 25 | 10.4% | 0.95 [0.39, 2.32] | |
Singh, 2016 | 111 | 217 | 189 | 223 | 13.2% | 0.19 [0.12, 0.30] | |
de Matos, 2019 | 67 | 101 | 61 | 98 | 12.5% | 1.20 [0.67, 2.14] | |
Subtotal (95% CI) | 1007 | 1661 | 100.0% | 0.78 [0.46, 1.33] | |||
Total events | 571 | 1062 | |||||
Heterogeneity: Tau² = 0.51; Chi² = 59.21, df = 7 (p < 0.00001); I² = 88% | Test for overall effect: Z = 0.91 (p = 0.37) | ||||||
AA + TA vs. TT | Campa, 2007 | 113 | 153 | 657 | 898 | 13.5% | 1.04 [0.70, 1.53] |
Shimizu, 2008 | 38 | 69 | 53 | 91 | 11.9% | 0.88 [0.47, 1.65] | |
Vairaktaris, 2008 | 102 | 156 | 72 | 156 | 13.1% | 2.20 [1.40, 3.48] | |
Kietthubthew, 2010 | 31 | 63 | 65 | 99 | 11.8% | 0.51 [0.27, 0.97] | |
Liu, 2012 | 173 | 270 | 230 | 350 | 13.8% | 0.93 [0.67, 1.30] | |
Hu, 2012 | 67 | 109 | 19 | 30 | 10.3% | 0.92 [0.40, 2.13] | |
Singh, 2016 | 194 | 300 | 266 | 300 | 13.2% | 0.23 [0.15, 0.36] | |
de Matos, 2019 | 91 | 125 | 93 | 130 | 12.5% | 1.06 [0.62, 1.84] | |
Subtotal (95%CI) | 1245 | 2054 | 100.0% | 0.83 [0.51, 1.35] | |||
Total events | 809 | 1455 | |||||
Heterogeneity: Tau² = 0.43; Chi² = 56.11, df = 7 (p < 0.00001); I² = 88% | Test for overall effect: Z = 0.76 (p = 0.45) | ||||||
AA vs. TT + TA | Campa, 2007 | 41 | 153 | 189 | 898 | 20.8% | 1.37 [0.93, 2.03] |
Vairaktaris, 2008 | 14 | 156 | 0 | 156 | 0.2% | 31.85 [1.88, 538.79] | |
Shimizu, 2008 | 8 | 69 | 8 | 91 | 3.2% | 1.36 [0.48, 3.83] | |
Kietthubthew, 2010 | 10 | 63 | 16 | 99 | 5.4% | 0.98 [0.41, 2.32] | |
Liu, 2012 | 42 | 270 | 66 | 350 | 25.1% | 0.79 [0.52, 1.21] | |
Hu, 2012 | 16 | 109 | 5 | 30 | 3.5% | 0.86 [0.29, 2.58] | |
Singh, 2016 | 83 | 300 | 77 | 300 | 28.8% | 1.11 [0.77, 1.59] | |
de Matos, 2019 | 24 | 125 | 32 | 130 | 13.1% | 0.73 [0.40, 1.32] | |
Subtotal (95%CI) | 1245 | 2054 | 100.0% | 1.10 [0.90, 1.33] | |||
Total events | 238 | 393 | |||||
Heterogeneity: Chi² = 11.21, df = 7 (p = 0.13); I² = 38% | Test for overall effect: Z = 0.95 (p = 0.34) |
Genetic Model | First Author, Publication Year | Case | Control | Weight | Odds Ratio | ||
---|---|---|---|---|---|---|---|
Events | Total | Events | Total | M-H, Random, 95%CI | |||
C vs. G | Vairaktaris, 2008 | 138 | 324 | 72 | 312 | 25.5% | 2.47 [1.75, 3.49] |
Gaur, 2011 | 49 | 280 | 69 | 240 | 24.9% | 0.53 [0.35, 0.80] | |
Singh, 2015 | 143 | 544 | 65 | 370 | 25.6% | 1.67 [1.20, 2.32] | |
Fernández-Mateos, 2019 | 83 | 140 | 101 | 140 | 24.0% | 0.56 [0.34, 0.93] | |
Subtotal (95%CI) | 1288 | 1062 | 100.0% | 1.07 [0.50, 2.26] | |||
Total events | 413 | 307 | |||||
Heterogeneity: Tau² = 0.54; Chi² = 44.63, df = 3 (P < 0.00001); I² = 93% | Test for overall effect: Z = 0.17 (p = 0.87) | ||||||
CC vs. GG | Vairaktaris, 2008 | 18 | 60 | 6 | 96 | 24.7% | 6.43 [2.38, 17.37] |
Gaur, 2011 | 7 | 105 | 14 | 79 | 24.9% | 0.33 [0.13, 0.87] | |
Singh, 2015 | 21 | 171 | 9 | 138 | 25.9% | 2.01 [0.89, 4.54] | |
Fernández-Mateos, 2019 | 25 | 37 | 39 | 47 | 24.5% | 0.43 [0.15, 1.19] | |
Subtotal (95%CI) | 373 | 360 | 100.0% | 1.17 [0.31, 4.36] | |||
Total events | 71 | 68 | |||||
Heterogeneity: Tau² = 1.57; Chi² = 23.28, df = 3 (P < 0.0001); I² = 87% | Test for overall effect: Z = 0.23 (p = 0.82) | ||||||
GC vs. GG | Vairaktaris, 2008 | 102 | 144 | 60 | 150 | 26.7% | 3.64 [2.24, 5.92] |
Gaur, 2011 | 35 | 130 | 41 | 106 | 26.0% | 0.58 [0.34, 1.01] | |
Singh, 2015 | 101 | 251 | 47 | 176 | 27.4% | 1.85 [1.22, 2.81] | |
Fernández-Mateos, 2019 | 33 | 45 | 23 | 31 | 20.0% | 0.96 [0.34, 2.71] | |
Subtotal (95% CI) | 570 | 463 | 100.0% | 1.44 [0.64, 3.26] | |||
Total events | 271 | 171 | |||||
Heterogeneity: Tau² = 0.59; Chi² = 25.23, df = 3 (P < 0.0001); I² = 88% | Test for overall effect: Z = 0.87 (p = 0.38) | ||||||
CC + GC vs. GG | Vairaktaris, 2008 | 120 | 162 | 66 | 156 | 26.1% | 3.90 [2.43, 6.26] |
Gaur, 2011 | 42 | 140 | 55 | 120 | 25.8% | 0.51 [0.30, 0.84] | |
Singh, 2015 | 122 | 272 | 56 | 185 | 26.6% | 1.87 [1.26, 2.78] | |
Fernández-Mateos, 2019 | 58 | 70 | 62 | 70 | 21.6% | 0.62 [0.24, 1.63] | |
Subtotal (95%CI) | 644 | 531 | 100.0% | 1.28 [0.50, 3.26] | |||
Total events | 342 | 239 | |||||
Heterogeneity: Tau² = 0.82; Chi² = 37.38, df = 3 (P < 0.00001); I² = 92% | Test for overall effect: Z = 0.51 (p = 0.61) | ||||||
CC vs. GG + GC | Vairaktaris, 2008 | 18 | 162 | 6 | 156 | 23.8% | 3.13 [1.21, 8.09] |
Gaur, 2011 | 7 | 140 | 14 | 120 | 23.9% | 0.40 [0.16, 1.02] | |
Singh, 2015 | 21 | 272 | 9 | 185 | 25.5% | 1.64 [0.73, 3.66] | |
Fernández-Mateos, 2019 | 25 | 70 | 39 | 70 | 26.9% | 0.44 [0.22, 0.87] | |
Subtotal (95%CI) | 644 | 531 | 100.0% | 0.96 [0.37, 2.50] | |||
Total events | 71 | 68 | |||||
Heterogeneity: Tau² = 0.77; Chi² = 15.80, df = 3 (P = 0.001); I² = 81% | Test for overall effect: Z = 0.09 (p = 0.93) |
Subgroups (N) | A vs. T | AA vs. TT | TA vs. TT | AA + TA vs. TT | AA vs. TT + TA | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | |
Overall (8) | 0.97 | [0.76, 1.23] | 0.78 | <0.0001 | 0.86 | [0.53, 1.41] | 0.55 | 0.001 | 0.78 | [0.46, 1.33] | 0.37 | <0.00001 | 0.83 | [0.51, 1.35] | 0.45 | <0.00001 | 1.10 | [0.90, 1.33] | 0.34 | 0.13 |
Ethnicity | ||||||||||||||||||||
Caucasian (3) | 1.11 | [0.61, 2.00] | 0.73 | <0.00001 | 1.35 | [0.31, 5.80] | 0.69 | <0.00001 | 069 | [0.19, 2.56] | 0.58 | <0.00001 | 0.81 | [0.23, 2.84] | 0.74 | <0.00001 | 1.40 | [0.78, 2.50] | 0.26 | 0.05 |
Asian (4) | 0.88 | [0.74, 1.06] | 0.17 | 0.73 | 0.81 | [0.56, 1.18] | 0.27 | 0.86 | 0.85 | [0.65, 1.11] | 0.23 | 0.28 | 0.84 | [0.65, 1.08] | 0.17 | 0.42 | 0.87 | [0.62, 1.23] | 0.44 | 0.81 |
Mixed (1) | 0.92 | [0.65, 1.30] | 0.64 | - | 0.82 | [0.40, 1.65] | 0.57 | - | 1.20 | [0.67, 2.14] | 0.55 | - | 1.06 | [0.62, 1.84] | 0.82 | - | 0.73 | [0.40, 1.32] | 0.30 | - |
Source of control | ||||||||||||||||||||
Population-based (7) | 0.97 | [0.74, 1.26] | 0.82 | <0.0001 | 0.87 | [0.51, 1.50] | 0.62 | 0.0005 | 0.76 | [0.43, 1.37] | 0.36 | <0.00001 | 0.82 | [0.48, 1.40] | 0.46 | <0.00001 | 1.11 | [0.91, 1.35] | 0.31 | 0.09 |
Hospital-based (1) | 0.92 | [0.51, 1.65] | 0.79 | - | 0.84 | [0.25, 2.79] | 0.77 | - | 0.95 | [0.39, 2.32] | 0.92 | - | 0.92 | [0.40, 2.13] | 0.85 | - | 0.86 | [0.29, 2.58] | 0.79 | - |
Genotyping method | ||||||||||||||||||||
PCR-RFLP (3) | 1.02 | [0.59, 1.78] | 0.94 | <0.00001 | 0.94 | [0.28, 3.18] | 0.92 | 0.0003 | 0.71 | [0.20, 2.49] | 0.59 | <0.00001 | 0.78 | [0.24, 2.55] | 0.68 | <0.00001 | 1.14 | [0.57, 2.28] | 0.71 | 0.02 |
TaqMan (3) | 0.99 | [0.83, 1.19] | 0.95 | 0.17 | 1.04 | [0.72, 1.49] | 0.84 | 0.33 | 0.83 | [0.51, 1.35] | 0.46 | 0.11 | 0.91 | [0.68, 1.20] | 0.50 | 0.14 | 1.10 | [0.81, 1.50] | 0.53 | 0.21 |
Other (2) | 0.96 | [0.67, 1.39] | 0.84 | 0.85 | 1.03 | [0.46, 2.33] | 0.93 | 0.65 | 0.86 | [0.51, 1.47] | 0.59 | 0.78 | 0.89 | [0.54, 1.48] | 0.67 | 0.93 | 1.10 | [0.51, 2.35] | 0.81 | 0.55 |
Subgroups (N) | C vs. G | CC vs. GG | GC vs. GG | CC + GC vs. GG | CC vs. GG + GC | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | OR | 95%CI | P | Ph | |
Overall (4) | 1.07 | [0.50, 2.26] | 0.87 | <0.00001 | 1.17 | [0.31, 4.36] | 0.82 | <0.0001 | 1.44 | [0.64, 3.26] | 0.38 | <0.0001 | 1.28 | [0.50, 3.26] | 0.61 | <0.00001 | 0.96 | [0.37, 2.50] | 0.93 | 0.001 |
Ethnicity | ||||||||||||||||||||
Caucasian (3) | 1.07 | [0.50, 2.26] | 0.87 | <0.00001 | 1.17 | [0.31, 4.36] | 0.82 | <0.0001 | 1.44 | [0.64, 3.26] | 0.38 | <0.0001 | 1.28 | [0.50, 3.26] | 0.61 | <0.00001 | 0.96 | [0.37, 2.50] | 0.93 | 0.001 |
Source of control | ||||||||||||||||||||
Population-based (2) | 2.03 | [1.38, 2.97] | 0.0003 | 0.11 | 0.96 | [0.21, 4.35] | 0.95 | 0.02 | 2.56 | [1.32, 4.99] | 0.005 | 0.04 | 2.67 | [1.30, 5.47] | 0.007 | 0.02 | 0.96 | [0.37, 2.50] | 0.93 | 0.001 |
Hospital-based (2) | 0.54 | [0.39, 0.74] | 0.0002 | 0.84 | 1.46 | [0.08, 26.60] | 0.80 | <0.0001 | 0.65 | [0.40, 1.06] | 0.08 | 0.41 | 0.53 | [0.34, 0.83] | 0.006 | 0.71 | 0.43 | [0.25, 0.74] | 0.002 | 0.86 |
Genotyping method | ||||||||||||||||||||
PCR-RFLP (3) | 1.31 | [0.56, 3.04] | 0.54 | <0.00001 | 0.68 | [0.21, 2.19] | 0.51 | 0.009 | 1.59 | [0.61, 4.19] | 0.35 | <0.00001 | 1.55 | [0.53, 4.59] | 0.43 | <0.00001 | 1.27 | [0.41, 3.97] | 0.68 | 0.008 |
TaqMan (1) | 0.56 | [0.34, 0.93] | 0.02 | - | 6.43 | [2.38, 17.37] | 0.0002 | - | 0.96 | [0.34, 2.71] | 0.93 | - | 0.62 | [0.24, 1.63] | 0.34 | - | 0.44 | [0.22, 0.87] | 0.02 | - |
Polymorphism | Variable | Allele Model | Homozygote Model | Heterozygote Model | Recessive Model | Dominant Model | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
R | Adjusted R2 | P | R | Adjusted R2 | P | R | Adjusted R2 | P | R | Adjusted R2 | P | R | Adjusted R2 | P | ||
IL-8 (-251T/A) | Year of publication | 0.484 | 0.106 | 0.225 | 0.348 | −0.025 | 0.398 | 0.239 | −0.100 | 0.569 | 0.374 | −0.003 | 0.361 | 0.351 | −0.023 | 0.395 |
IL-6 (-174G/C) | 0.594 | 0.030 | 0.406 | 0.913 | 0.751 | 0.087 | 0.595 | 0.032 | 0.405 | 0.653 | 0.140 | 0.347 | 0.645 | 0.125 | 0.355 | |
IL-8 (-251T/A) | Number of participants | 0.022 | −0.166 | 0.959 | 0.122 | −0.149 | 0.773 | 0.111 | −0.152 | 0.794 | 0.069 | −0.161 | 0.872 | 0.307 | −0.057 | 0.460 |
IL-6 (-174G/C) | 0.616 | 0.069 | 0.384 | 0.585 | 0.014 | 0.415 | 0.414 | −0.243 | 0.586 | 0.462 | −0.180 | 0.538 | 0.516 | −0.100 | 0.484 |
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Rezaei, F.; Mohammadi, H.; Heydari, M.; Sadeghi, M.; Mozaffari, H.R.; Khavid, A.; Godiny, M.; Brand, S.; M. Dürsteler, K.; Beatrix Brühl, A.; et al. Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis. Medicina 2021, 57, 405. https://doi.org/10.3390/medicina57050405
Rezaei F, Mohammadi H, Heydari M, Sadeghi M, Mozaffari HR, Khavid A, Godiny M, Brand S, M. Dürsteler K, Beatrix Brühl A, et al. Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis. Medicina. 2021; 57(5):405. https://doi.org/10.3390/medicina57050405
Chicago/Turabian StyleRezaei, Farzad, Hady Mohammadi, Mina Heydari, Masoud Sadeghi, Hamid Reza Mozaffari, Atefeh Khavid, Mostafa Godiny, Serge Brand, Kenneth M. Dürsteler, Annette Beatrix Brühl, and et al. 2021. "Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis" Medicina 57, no. 5: 405. https://doi.org/10.3390/medicina57050405