Association betweenNFKB1−94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis

Abstract

Nuclear factor-κB is associated with the pathogenesis of numerous malignancies, and the functional polymorphism −94ins/del ATTG (rs28362491) in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the −94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. We found that the NFKB1 promoter −94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35). Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.

Interactions between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases among the Japanese population

“… 14 A common deletion-allele in the promoter region of NF- κ B 1 results in lower protein levels of the NF-κB p50 subunit. NF- κ B1 94ATTG ins/del polymorphism was associated with risk of cancer 32 , 33 and CHD. 37 However, the present study did not find an interaction between NF- κ B1 94ATTG ins/del polymorphism and HTLV-I for the risk of total death or incidence of cancer and atherosclerosis-related diseases.…”

“…The associations between inflammatory gene polymorphisms and the development of ATLL 23 and HAM/TSP has been reported. 24 , 25 , 26 , 27 Interestingly, these polymorphisms were also associated with the development of not only several sites of cancer, 28 , 29 , 30 , 31 , 32 , 33 but also atherosclerosis-related diseases. 34 , 35 , 36 , 37 TNF- α , encoded by the TNF -α gene, is a cytokine responsible for resistance to infection and cancers and exerts major proinflammatory action by stimulating adhesion molecules and chemokine expression.…”

“…We selected three single-nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) greater than 0.05 from the common genes for cytokines that have important roles in the immune-inflammatory processes of HTLV-I infection, cancers, and atherosclerosis, including TNF -α 1031T/C [rs1799964], IL-10 819T/C [rs1800871], and NF- κ B1 94ATTG ins/del [rs28362491]. 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 These SNPs were genotyped using TaqMan allelic discrimination kits (Applied Biosystems, Foster City, CA, USA) and real-time polymerase chain reaction (StepOne, Applied Biosystems). Each reaction was performed in a 10 μL volume that contained 1 μL of genomic DNA (10 mg/μL), 5 μL of TaqMan Universal PCR Master Mix II, 0.125 μL of 40 × genotyping assay mix, and 3.875 μL of dH 2 O.…”

Lipid Metabolism is Closely Associated with Normal Testicular Growth Based on Global Transcriptome Profiles in Normal and Underdeveloped Testis of Obese Zucker (fa/fa) Rats

“…5), on the other hand, were connected with cancer, specifically prostate cancer signaling, and leptin signaling in obesity. Polymorphisms in nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) have been associated with development of prostate cancer [44,45].…”

Association of the genetic polymorphisms of NFKB1 with susceptibility to ovarian cancer

“…As a polygenic disease, the pathogen esis of ovarian cancer is multifactorial, which means that multiple genetic factors may be associated with its development and progression (Gulden and Olopade, 2010). Previous studies have suggested that polymorphisms in nuclear factor-kB (NF-kB), a transcription factor that is activated by various stimuli, may be associated with ovarian cancer (Yang et al, 2014).…”