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Association of IL-8 gene promoter -251 A/T and IL-18 gene promoter -137 G/C polymorphisms with head and neck cancer risk: a comprehensive meta-analysis

Authors Wang Z, Gao ZM, Huang HB, Sun LS, Sun AQ, Li K

Received 15 February 2018

Accepted for publication 13 April 2018

Published 10 August 2018 Volume 2018:10 Pages 2589—2604

DOI https://doi.org/10.2147/CMAR.S165631

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Zheng Wang,1 Zi-Ming Gao,2 Hai-Bo Huang,2 Li-Sha Sun,2 An-Qi Sun,2 Kai Li2

1Department of Otorhinolaryngology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China; 2 Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China

Purpose: No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC).
Methods: Thus, a meta-analysis including 22 studies with 4731 cases and 8736 controls was conducted to evaluate this association. The summary odds ratio (OR) and corresponding 95% confidence intervals (CIs) for C-X-C motif chemokine ligand 8 (CXCL8, which encodes IL-8) and IL-18 polymorphisms and HNC risk were estimated.
Results: The results showed a significantly increased risk of HNC susceptibility for IL18-137 G/C in five genetic models, but, interestingly, no significant association was found for the CXCL8-251 A/T polymorphism. When stratified by cancer type, an increased risk of nasopharyngeal cancer was found for both -137 G/C and -251A/T. When the studies were stratified by ethnicity and genotyping method, there were significant associations between Asian populations and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) studies for -137 G/C, and African populations for -251 A/T in some genetic models. A positive association was also found between the population-based groups in some models for -137 G/C; conversely, significantly decreased risk was found among the -251 A/T hospital-based group. Meta-regression was also conducted. The publication year, control source, and cancer type contributed to CXCL8 -251 A/T heterogeneity; however, no factors were found that contributed to IL-18 -137 G/C heterogeneity. Marginal significance was found in the recessive model for IL-18 -137 G/C by Egger’s test, whereas no publication bias was detected for CXCL8 -251 A/T.
Conclusions: The results indicate that the IL-18 -137 G/C polymorphism is associated with HNC risk, especially nasopharyngeal cancer, in Asian populations and, when using PCR-RFLP, CXCL8 -251 A/T polymorphisms play a complex role in HNC development.

Keywords: interleukin-8, interleukin-18, polymorphism, head and neck cancer, meta-analysis

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