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.
Highlights
Cancer is a major public health problem worldwide; it is the primary and secondary causes of death in economically developed and developing countries, respectively [1]
The allele and genotype frequencies of the NFKB1 promoter −94ins/del ATTG polymorphism were extracted from all eligible studies
The pooled odds ratios (ORs) of the included case-control studies revealed a statistically significant association between the NFKB1 promoter −94ins/del ATTG polymorphism and cancer risk across the four genetic models ins/ins versus del/del, OR=1.47, 95%, CI=1.11—1.93; dominant model, OR=1.26, 95% confidence intervals (95% CIs)=1.03—1.53; recessive model, OR=1.26,95% CI=1.05—1.51; and ins allele versus del allele, OR=1.19,95%, CI=1.05–1.35 (Table 2, Figure 2)
Summary
Cancer is a major public health problem worldwide; it is the primary and secondary causes of death in economically developed and developing countries, respectively [1]. Nuclear factor-κB (NF-κB) was initially identified in 1986 as a transcription factor which binds to a 10 bp DNA element in kappa immunoglobulin light-chain enhancer in B cells [3]. The major form of NF-κB is a heterodimer of the p50 and p65/RelA subunits which are encoded by the NFKB1 and NFKB2 genes, respectively [4]. The human NFKB1 gene is mapped to chromosome 4q24 and encodes a 50 kDa DNA-binding protein (p50) that can act as a master regulator of inflammation and cancer development [5,6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
