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


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.
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Meng
M
Zhang
Department of Medicine, Shenzhen University, Shenzhen, Anhui, China (mainland).
Junjie
J
Huang
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Xiuxiu
X
Tan
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Jian
J
Bai
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Hao
H
Wang
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Yukun
Y
Ge
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Hu
H
Xiong
Department of Medicine, Shengli Oilfield Central Hospital, Dongying, Shandong, China (mainland).
Jizhou
J
Shi
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Wei
W
Lu
Department of Urology, Shenzhen Second People's Hospital, Clinical Medicine College of Anhui Medical University, Shenzhen, Anhui, China (mainland).
Zhaojie
Z
Lv
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Chaozhao
C
Liang
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D007107:Immune System; D007249:Inflammation; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D009369:Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha