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Common Polymorphisms in the NFKBIA Gene and Cancer Susceptibility: A Meta-Analysis

Meng Zhang, Junjie Huang, Xiuxiu Tan, Jian Bai, Hao Wang, Yukun Ge, Hu Xiong, Jizhou Shi, Wei Lu, Zhaojie Lv, Chaozhao Liang

Department of Urology, Shenzhen Second People’s Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland)

Med Sci Monit 2015; 21:3186-3196

DOI: 10.12659/MSM.895257

Available online:

Published: 2015-10-21

BACKGROUND: NFKBIA encodes the inhibitors of nuclear factor-κB (NF-κB), which regulate the translation of the genes involved in the inflammatory and immune reactions. Polymorphisms (rs2233406, rs3138053, and rs696) of NFKBIA have been implicated in susceptibility to many cancer types.
MATERIAL AND METHODS: To evaluate the association between polymorphisms of NFKBIA and cancer susceptibility, a meta-analysis including a total of 7182 cancer cases and 10 057 controls from 28 case-control studies was performed. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
RESULTS: Combined data demonstrated that rs3138053 polymorphism of NFKBIA was associated with cancer susceptibility in an allelic model (C vs. T: OR=10.754, 95%CI=4.175–27.697, Pheterogeneity=0.000), while the polymorphism of rs696 appeared to play a protective role in tumorigenesis (CC+CT vs. TT: OR=0.879, 95%CI=0.787–0.982, Pheterogeneity=0.107). When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970–63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656–0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448–0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562–0.958, Pheterogeneity=0.347). By ethnicity, rs696 appears to be a protective candidate among Caucasians (CT vs. TT: OR=0.809, 95%CI=0.676–0.969, Pheterogeneity=0.459).
CONCLUSIONS: Our data demonstrated that the rs3138053 polymorphism of NFKBIA gene is a candidate for susceptibility to overall cancers, while rs696 plays a protective role.

Keywords: Case-Control Studies, Alleles, Genetic Predisposition to Disease, Hodgkin Disease - genetics, I-kappa B Proteins - genetics, Immune System, Inflammation, Neoplasms - genetics, Odds Ratio, Polymorphism, Single Nucleotide