NF-kB2 Genetic Variations are Significantly Associated with Non-Small Cell Lung Cancer Risk and Overall Survival

Foteinos Ioannis D. Dimitrakopoulos, Anna G. Antonacopoulou, Anastasia E. Kottorou, Stella Maroussi, Nikolaos Panagopoulos, Ioulia Koukourikou, Chrisoula Scopa, Melpomeni Kalofonou, Angelos Koutras, Thomas Makatsoris, Helen Papadaki, Dimitrios Dougenis, Malcolm V Brock, Haralabos P. Kalofonos

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5259
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

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    Dimitrakopoulos, F. I. D., Antonacopoulou, A. G., Kottorou, A. E., Maroussi, S., Panagopoulos, N., Koukourikou, I., Scopa, C., Kalofonou, M., Koutras, A., Makatsoris, T., Papadaki, H., Dougenis, D., Brock, M. V., & Kalofonos, H. P. (2018). NF-kB2 Genetic Variations are Significantly Associated with Non-Small Cell Lung Cancer Risk and Overall Survival. Scientific Reports, 8(1), [5259]. https://doi.org/10.1038/s41598-018-23324-3