title: Functional polymorphisms in NFκB1/IκBα predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.
abstract: Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/IκB confer consistent risks for COPD and lung cancer. Four putative functional SNPs (NFκB1: -94del>insATTG; NFκB2: -2966G>A; IκBα: -826C>T, 2758G>A) were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the -94ins ATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of COPD (OR 1.27, 95% CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline (P = 0.015). The 2758AA variant in IκBα had an increased risk of lung cancer (OR 1.53, 95% CI 1.30-1.80) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the -94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for -2966G>A and -826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFκB1 (-94del>ins ATTG) or IκBα (2758G>A) to predict risk of COPD or lung cancer.
authors: School of Public Health, The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors: Dongsheng
authors: D
authors: Huang
authors: Lei
authors: L
authors: Yang
authors: Yehua
authors: Y
authors: Liu
authors: Yumin
authors: Y
authors: Zhou
authors: Yuan
authors: Y
authors: Guo
authors: Mingan
authors: M
authors: Pan
authors: Yunnan
authors: Y
authors: Wang
authors: Yigang
authors: Y
authors: Tan
authors: Haibo
authors: H
authors: Zhong
authors: Min
authors: M
authors: Hu
authors: Wenju
authors: W
authors: Lu
authors: Weidong
authors: W
authors: Ji
authors: Jian
authors: J
authors: Wang
authors: Pixin
authors: P
authors: Ran
authors: Nanshan
authors: N
authors: Zhong
authors: Yifeng
authors: Y
authors: Zhou
authors: Jiachun
authors: J
authors: Lu
mesh_terms: D044466:Asian People; D002681:China / Q000453:epidemiology; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D052003:NF-kappa B p52 Subunit / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D020672:I-kappa B Proteins; C522425:MIRN34 microRNA, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; C489548:NFKB1 protein, human; C498206:NFKB2 protein, human; D009363:Neoplasm Proteins