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Abstract
During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively). Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028, respectively), especially among patients with stages III/IV, who had worse 2, 3 and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also associated with worse 2- and 3-year survival compared to G allele carriers (P = 0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with survival outcome of stage I and II patients (P = 0.031 and P = 0.006, respectively). Interestingly, amongst the patients who developed metastases, A allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025). Overall, this study suggests that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment response and in clinical outcome.
Highlights
Rs7897947, rs11574852 and rs12769316 in Non-small cell lung cancer (NSCLC) and their association with NF-kB2 protein and mRNA levels
No difference was observed in allele specific frequencies between NSCLC patients and healthy controls, an increased risk for NSCLC was noted for the rs7897947 TT genotype compared to the G allele carriers (Table 1)
Three SNPS of the NF-kB2 gene were evaluated in NSCLC patients and healthy controls through monitoring of their association with NF-kB2 expression, clinicopathological parameters and clinical outcome of the patients
Summary
Rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. A great variety of genes and signalling pathways have been implicated in the development and progression of human lung cancer, the role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) has become an object of intense study in epithelial lung malignancies[6,7,8] only in the last decade[6,7,8]. This transcription factor has been characterized as a “double-edged sword” since, on the one hand, its role is important for the Baltimore, MD, USA. Two of the central players are p100/p52 and RelB, which together give rise to a transcriptionally active heterodimer (Fig. 1A)
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