title: Association and interaction of NFKB1 rs28362491 insertion/deletion ATTG polymorphism and PPP1R13L and CD3EAP related to lung cancer risk in a Chinese population.
abstract: The nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NFKB1) gene encodes p105 and p50 kD which are both subunits of the transcription factor NF-kB, involved in a wide variety of diseases and pathological states associated with inflammation, immunity, and tumorigenesis. The NFKB1 rs28362491 polymorphism in the promoter region (-94 insertion/deletion ATTG) has been associated with risk of various cancers. Our study aims were to evaluate the associations of NFKB1 rs28362491 polymorphism and interactions of this single-nucleotide polymorphism (SNP) and PPP1R13L and CD3EAP and smoking duration in relation to lung cancer risk in a Chinese population. The study population consisted of 544 Chinese lung cancer cases and 550 cancer-free matched (age, sex, and ethnicity) controls. No associations were found between NFKB1 rs28362491 and lung cancer risk. CD3EAP rs967591 was associated with increased lung cancer risk in the dominant model [OR (95 % CI) = 1.38 (1.05-1.80), P = 0.018]. The common haplotype containing PPP1R13L rs1970764(G), CD3EAP rs967591(A), and CD3EAP rs735482(C) was associated with lung cancer [adjusted OR (95 % CI) = 1.29 (1.03-1.62), P = 0.028]. Multifactor dimensionality reduction (MDR) analysis revealed two-way and three-way interactions between CD3EAP rs735482 and smoking and between NFKB1 rs28362491, PPP1R13L rs1970764, and smoking. In conclusion, we were able to reproduce previously found associations between PPP1R13L and CD3EAP polymorphisms and lung cancer risk in an increased study group, and we found interactions between NFKB1 rs28362491-PPP1R13L rs1970764 and smoking duration and between CD3EAP rs735482 and smoking duration. These results suggest that these genes and smoking are part of the same biological pathway leading to smoking-induced lung cancer.
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, 110034, Liaoning, People's Republic of China. yinjye@163.com.
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Yin
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, 110034, Liaoning, People's Republic of China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Research Centre for the Working Environment, Lerso Parkalle 105, DK-2100, Copenhagen O, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, 110034, Liaoning, People's Republic of China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Thoracic Surgery, Liaoning Cancer Hospital, Shenyang, 110042, Liaoning, People's Republic of China.
authors.forename: Yegang
authors.initials: Y
authors.lastname: Ma
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012318:RNA Polymerase I; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I
keywords: Chinese; Interaction; Lung cancer; NFKB1 rs28362491 and PPP1R13L and CD3EAP; Single-nucleotide polymorphisms