Association Between the<i>NFKB1</i>-94ins/del ATTG Polymorphism and Cancer Risk: An Updated Meta-Analysis

Duan, Wei; Wang, Erli; Zhang, Fengquan; Wang, Tongjian; You, Xiang-Dong; Qiao, Bin

doi:10.3109/07357907.2014.911881

Cited by 17 publications

(15 citation statements)

References 48 publications

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“…This notion is consistent with a recent study showing that the reduced lifespan of nfkb1 −/− mice could be attributed to chronic, progressive low‐grade inflammation and premature ageing 14 . Interestingly, in humans (certain Asian populations) the NF‐κB1 ‐94ins/del promoter polymorphism, resulting in reduced NF‐κB1 protein expression, is associated with increased cancer risk 44 . Thus, constitutive drug‐mediated inhibition of NF‐κB1 may exacerbate certain autoimmune pathologies by increasing inflammation and may also increase the risk of malignancy.…”

Section: Discussionsupporting

confidence: 91%

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice

et al. 2015

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Defects in apoptosis can cause autoimmune disease. Loss-of-function mutations in the 'death receptor' FAS impair the deletion of autoreactive lymphocytes in the periphery, leading to progressive lymphadenopathy and systemic lupus erythematosus-like autoimmune disease in mice (Fas(lpr/lpr) (mice homozygous for the lymphoproliferation inducing spontaneous mutation)) and humans. The REL/nuclear factor-κB (NF-κB) transcription factors regulate a broad range of immune effector functions and are also implicated in various autoimmune diseases. We generated compound mutant mice to investigate the individual functions of the NF-κB family members NF-κB1, NF-κB2 and c-REL in the various autoimmune pathologies of Fas(lpr/lpr) mutant mice. We show that loss of each of these transcription factors resulted in amelioration of many classical features of autoimmune disease, including hypergammaglobulinaemia, anti-nuclear autoantibodies and autoantibodies against tissue-specific antigens. Remarkably, only c-REL deficiency substantially reduced immune complex-mediated glomerulonephritis and extended the lifespan of Fas(lpr/lpr) mice. Interestingly, compared with the Fas(lpr/lpr) animals, Fas(lpr/lpr)nfkb2(-/-) mice presented with a dramatic acceleration and augmentation of lymphadenopathy that was accompanied by severe lung pathology due to extensive lymphocytic infiltration. The Fas(lpr/lpr)nfkb1(-/-) mice exhibited the combined pathologies caused by defects in FAS-mediated apoptosis and premature ageing due to loss of NF-κB1. These findings demonstrate that different NF-κB family members exert distinct roles in the development of the diverse autoimmune and lymphoproliferative pathologies that arise in Fas(lpr/lpr) mice, and suggest that pharmacological targeting of c-REL should be considered as a strategy for therapeutic intervention in autoimmune diseases.

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Section: Discussionsupporting

confidence: 91%

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice

et al. 2015

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“…These findings were also specific to the Asian population. Duan et al [31] reviewed a total of 25 studies that included 8,750 cancer cases and 9,170 controls. They found that the insertion allele of the -94ins/delATTG polymorphism significantly increased cancer risk, both in overall genetic analysis as well as in Asians.…”

Section: Discussionmentioning

confidence: 99%

NFKB1-94insertion/deletion ATTG polymorphism and cancer risk: Evidence from 50 case-control studies

Zhang

Chen

et al. 2016

Oncotarget

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Nuclear factor-kappa B1 (NF-κB1) is a pleiotropic transcription factor and key contributor to tumorigenesis in many types of cancer. Numerous studies have addressed the association of a functional insertion (I)/deletion (D) polymorphism (-94ins/delATTG, rs28362491) in the promoter region of NFKB1 gene with the risk of various types of cancer; however, their conclusions have been inconsistent. We therefore conducted a meta-analysis to reevaluate this association. PubMed, EMBASE, China National Knowledge infrastructure (CNKI), and WANFANG databases were searched through July 2016 to retrieve relevant studies. After careful assessment, 50 case-control studies, comprising 18,299 cases and 23,484 controls were selected. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to determine the strength of the association. The NFKB1 -94ins/delATTG polymorphism was associated with a decreased risk of overall cancer in the homozygote model (DD vs. II): OR = 0.75, 95% CI = 0.64-0.87); heterozygote model (ID vs. II): OR = 0.91, 95% CI = 0.83-0.99; recessive model (DD vs. ID/II): OR = 0.81, 95% CI = 0.71-0.91; dominant model (ID/DD vs. II): OR = 0.86, 95% CI = 0.78-0.95; and allele contrast model (D vs. I): OR = 0.88, 95% CI = 0.81-0.95). Subgroup and stratified analyses revealed decreased risks for lung cancer, nasopharyngeal carcinoma, prostate cancer, ovarian cancer, and oral squamous cell carcinoma, and this association held true also for Asians (especially Chinese subjects) in hospital-based studies, and in studies with quality scores less than nine. Well-designed, large-scale case-control studies are needed to confirm these results.

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“…Previous studies have reported that geographical, lifestyle and ethnic differences can impact on genetic/molecular pathways in head and neck squamous cancers [32–37]. Majority of these studies investigated genetic DNA polymorphisms but none of them, to our knowledge, compared gene expression levels in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas

Dai

Duan

et al. 2016

Oncotarget

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The forkhead box M1 (FOXM1) transcription factor gene has been implicated in almost all human cancer types. It would be an ideal biomarker for cancer detection but, to date, its translation into a cancer diagnostic tool is yet to materialise. The quantitative Malignancy Index Diagnostic System (qMIDS) was the first FOXM1 oncogene-based diagnostic test developed for quantifying squamous cell carcinoma aggressiveness. The test was originally validated using head and neck squamous cell carcinomas (HNSCC) from European patients. The HNSCC gene expression signature across geographical and ethnic differences is unknown. This is the first study evaluated the FOXM1-based qMIDS test using HNSCC specimens donated by ethnic Chinese patients. We tested 50 Chinese HNSCC patients and 18 healthy subjects donated 68 tissues in total. qMIDS scores from the Chinese cohort were compared with the European datasets (n = 228). The median ± SD scores for the Chinese cohort were 1.13 ± 0.66, 4.02 ± 1.66 and 5.83 ± 3.13 in healthy oral tissues, adjacent tumour margin and HNSCC core tissue, respectively. Diagnostic test efficiency between the Chinese and European datasets was almost identical. Consistent with previous European data, qMIDS scores for HNSCC samples were not influenced by gender or age. The degree of HNSCC differentiation, clinical stage and lymphatic metastasis status were found to be correlated with qMIDS scores. This study provided the first evidence that the pathophysiology of HNSCC was molecularly indistinguishable between the Chinese and European specimens. The qMIDS test robustly quantifies a universal FOXM1-driven oncogenic program, at least in HNSCC, which transcends ethnicity, age, gender and geographic origins.

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Association Between theNFKB1-94ins/del ATTG Polymorphism and Cancer Risk: An Updated Meta-Analysis

Cited by 17 publications

References 48 publications

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice

NFKB1-94insertion/deletion ATTG polymorphism and cancer risk: Evidence from 50 case-control studies

Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas

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Association Between theNFKB1-94ins/del ATTG Polymorphism and Cancer Risk: An Updated Meta-Analysis

Cited by 17 publications

References 48 publications

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Faslpr/lpr mutant mice

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Faslpr/lpr mutant mice

NFKB1-94insertion/deletion ATTG polymorphism and cancer risk: Evidence from 50 case-control studies

Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas

Contact Info

Product

Resources

About

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice

Impact of loss of NF‐κB1, NF‐κB2 or c‐REL on SLE‐like autoimmune disease and lymphadenopathy in Fas^lpr/lpr mutant mice