title: The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-KB1 reduces the risk of BC.
abstract: Nuclear factor kappaB (NF-kB) plays a key role in mammary gland development and breast cancer (BC) progression. A functional -94 insertion/deletion ATTG polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to affect NF-KB1 expression and confer susceptibility to different types of cancer. The current study aimed to assess the association of NFKB1 -94 insertion/deletion ATTG promoter polymorphism and BC risk in an Iranian population. A total of 439 subjects including on 236 BC patients and 203 healthy women were recruited. The NF-KB1 -94ins/del ATTG polymorphism was genotyped by Allele-Specific polymerase chain reaction (AS-PCR) method. Our results demonstrated that the NF-KB1 -94ins/del ATTG polymorphism was associated with a reduced risk of BC in Codominant (Ins/Ins vs. Del/Del: OR = 0.33, 95%CI = 0.17-0.64; P= 0.001), dominant (Ins/Ins vs. Ins/Del+Del/Del: OR = 0.64, 95%CI = 0.42-0.97; P= 0.027) and recessive (Ins/Del+Del/Del vs. Del/Del: OR = 0.40, 95%CI = 0.21-0.75; P= 0.002) tested inheritance models. Additionally, the Del allele of NF-KB1 -94ins/del ATTG variation with a higher prevalence in the control group compared to the BC patients (43.3% vs. 33.5%) was associated with a decreased risk of BC (OR = 0.66, 95%CI = 0.50-0.86, P= 0.003). In conclusion, our findings for the first time, suggest that the NF-KB1 -94ins/del Del allele and Del/Del genotype were associated with a reduced risk of BC which may contribute as protective factors against BC.
authors.affiliation: Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.|Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
authors.affiliation: Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.|Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Shadi
authors.initials: S
authors.lastname: Amininia
mesh_terms: D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D052002:NF-kappa B p50 Subunit
keywords: NF-kB; breast cancer; deletion polymorphism