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

Abstract

BackgroundNFKBIA 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/MethodsTo 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.ResultsCombined 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).ConclusionsOur data demonstrated that the rs3138053 polymorphism of NFKBIA gene is a candidate for susceptibility to overall cancers, while rs696 plays a protective role.

Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients

“…All the analytical values were measured at ICU admission. IL-6 > 70 pg/mL and D-dimer > 2,000 ng/mL were considered as the cutoff values based on previous reports stating their relation to higher risk of death in COVID-19 [16] , [17] , [18] , [19] , [20] , [21] . Pre-existing hypertension, hyperlipidemia and diabetes were obtained from the medical records.…”

“…The NF-κB signaling depends tightly on the functionality of its components, both activators and inhibitors. Several polymorphisms in the genes encoding components of this pathway can predispose to an altered activation of NF-κB and have been associated with the risk of developing several inflammation-mediated diseases [16] , [17] , [18] , [19] . We hypothesized that common NF-κB variants might play a role in the risk of developing severe COVID-19.…”

CTLA-4 blockade and interferon-α induce proinflammatory transcriptional changes in the tumor immune landscape that correlate with pathologic response in melanoma

“…Lastly, changes in post-treatment gene expression were evaluated between samples available from radiologic responders (n = 8) vs. non-responders (n = 16). In radiologic responders, more than 10 genes such as NFKBIA, MARCO, CHIT1 (chitotriosidase 1), and TANK (TRAF family member associated NF-κB activator) demonstrated increased expression that were associated with radiologic response (unadjusted p < 0.01, S4A Fig) . Both NFKBIA, and TANK are involved in NF-κB activation, and common polymorphisms in NFKBIA is associated with susceptibility to cancer [61][62][63]. Chitinase is secreted by activated human macrophages, implicated in several types of cancers and inflammation [64].…”

Virtual Screening of Cablin Patchouli Herb as a Treatment for Heat Stress: A Study Based on Network Pharmacology, Molecular Docking, and Experimental Verification

“…Hypoxiainducible factor 1-alpha (HIF1A) is an oxygen-dependent transcriptional activator that plays key roles in tumor angiogenesis and mammalian development [57]. Finally, NFKBIA encodes inhibitors of nuclear factor-κB (NF-κB) that regulate the translation of genes involved in inflammatory and immune reactions [58,59]. In conclusion, our results demonstrate that EGFR, NCOA1, FOS, HIF1A, NFKBIA, and NCOA2 may be the main targets of CPB.…”