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

Abstract

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.

Figure 1

Flow chart presenting the study selection procedure.

Figure 2A

Meta-analysis of the association between NFKBIA rs3138053 polymorphism and overall cancer susceptibility (C vs. T).

Figure 2B

Meta-analysis of the association between NFKBIA rs696 polymorphism and overall cancer susceptibility (CC+CT vs. TT).

Figure 2C

Subgroup analysis of the association between NFKBIA polymorphisms and overall cancer risk by HWE (Hardy-Weinberg equilibrium).

Figure 3A

Publication bias examinations by Begg’s funnel plots and Egger’s test (rs696: CC+CT vs. TT). Asymmetrical plots or P<0.10 suggest potential bias. Each point represents a separate study for the indicated association, and the horizontal line depicts mean effect size. Logor natural logarithm of OR; s.e. standard error.

Figure 3B

Publication bias examinations by Begg’s funnel plots and Egger’s test (rs2233406: CC vs. CT+TT). Asymmetrical plots or P<0.10 suggest potential bias. Each point represents a separate study for the indicated association, and the horizontal line depicts mean effect size. Logor natural logarithm of OR; s.e. standard error.