title: Polymorphisms of NFκB1 and IκBα and Their Synergistic Effect on Nasopharyngeal Carcinoma Susceptibility.
abstract: Nasopharyngeal carcinoma (NPC) is a multifactoral and polygenic disease with high prevalence in Southeast Asia and Southern China. Environmental factors and genetic susceptibility play important roles in NPC pathogenesis. In the present study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in nuclear factor-kappa B (NFκB) and its inhibitor (IκBα) conferred consistent risks for NPC. Four putatively functional SNPs (NFκB1: rs28362491del>ins ATTG; NFκB2: rs12769316G>A; IκBα: rs2233406C>T and rs696G>A) were analyzed to evaluate their associations with NPC risk in total 1590 NPC cases and 1979 cancer-free controls. We found that the rs28362491 insATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of NPC (odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.09-1.55, and P = 2.80 × 10(-3)) compared with the del/del homozygous genotype. The rs696AA variant in IκBα had an increased risk of NPC (OR = 1.41, 95% CI = 1.20-1.66, and P = 2.28 × 10(-5)) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a. Furthermore, both adverse genotypes of NFκB/IκBα and their interaction also exerted an increased risk on NPC. Taken together, Our findings indicated that genetic variants in NFκB1 (rs28362491del>ins ATTG) and IκBα (rs696G>A) and their synergistic effect might contribute to NPC predisposition.
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, Collaborative Innovation Center for Environmental Toxicity, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D001483:Base Sequence; D002277:Carcinoma; D016022:Case-Control Studies; D057075:Enzyme Assays; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D020672:I-kappa B Proteins; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D008156:Luciferases