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Open Access Research article

Association of interferon regulatory factor 4 gene polymorphisms rs12203592 and rs872071 with skin cancer and haematological malignancies susceptibility: a meta-analysis of 19 case–control studies

Songtao Wang1, Qing Yan1, Pin Chen1, Peng Zhao1* and Aihua Gu23*

Author Affiliations

1 Department of Neurosurgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China

2 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China

3 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

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BMC Cancer 2014, 14:410  doi:10.1186/1471-2407-14-410

Published: 6 June 2014

Abstract

Background

Research has indicated that the rs12203592 and rs872071 interferon regulatory factor 4 (IRF4) gene polymorphisms correlate with the risk of cancer, especially skin cancer and haematological malignancies, but the results remain controversial. To understand better the effects of these two polymorphisms on skin cancer and haematological malignancies susceptibility, a cumulative meta-analysis was performed.

Methods

We conducted a search using the PubMed and Web of Science databases for relevant case-control studies published before April 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using fixed- or random-effects models where appropriate. Heterogeneity test, publication bias test, and sensitivity analysis were also performed.

Results

In total, 11 articles comprised of 19 case–control studies were identified; five focused on the rs12203592 polymorphism with 7,992 cases and 8,849 controls, and six were on the rs872071 polymorphism with 3108 cases and 8300 controls. As for rs12203592, a significant correlation with overall skin cancer and haematological malignancies risk was found with the homozygote comparison model (OR = 1.566, 95% CI 1.087-2.256) and recessive model (OR = 1.526, 95% CI 1.107-2.104). For rs872071, a significantly elevated haematological malignancies risk was observed in all genetic models (homozygote comparison: OR = 1.805, 95% CI 1.402-2.323; heterozygote comparison: OR = 1.427, 95% CI 1.203-1.692; dominant: OR = 1.556, 95% CI 1.281-1.891; recessive: OR = 1.432, 95% CI 1.293-1.587; additive: OR = 1.349, 95% CI 1.201-1.515). Similarly, increased skin cancer and haematological malignancies risk was also identified after stratification of the SNP data by cancer type, ethnicity and source of controls for both polymorphisms.

Conclusions

Our meta-analysis indicated that the rs12203592 and rs872071 IRF4 gene polymorphisms are associated with individual susceptibility to skin cancer and haematological malignancies. Moreover, the effect of the rs12203592 polymorphism on skin cancer risk was particularly prominent among Caucasians. Further functional research should be performed to validate the association.

Keywords:
Meta-analysis; IRF4; Interferon regulatory factor 4; Polymorphisms; rs12203592; rs872071; Cancer risk