Oncotarget

Research Papers:

Individual and combined effect of TP53, MDM2, MDM4, MTHFR, CCR5, and CASP8 gene polymorphisms in lung cancer

Ausra Stumbryte _, Zivile Gudleviciene, Gabrielis Kundrotas, Daiva Dabkeviciene, Agne Kunickaite and Saulius Cicenas

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Oncotarget. 2018; 9:3214-3229. https://doi.org/10.18632/oncotarget.22756

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Abstract

Ausra Stumbryte1,2, Zivile Gudleviciene1, Gabrielis Kundrotas1, Daiva Dabkeviciene2, Agne Kunickaite3 and Saulius Cicenas4,5

1Biobank, National Cancer Institute, LT-08660 Vilnius, Lithuania

2Institute of Biosciences, Vilnius University Life Sciences Center, LT-10257 Vilnius, Lithuania

3Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania

4Department of Thoracic Surgery and Oncology, National Cancer Institute, LT-08660 Vilnius, Lithuania

5Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania

Correspondence to:

Ausra Stumbryte, email: ausra.stumbryte@nvi.lt

Keywords: lung cancer prognostic markers; SNPs; patient survival; mortality rate; HPV phylogenetic line

Received: March 22, 2017     Accepted: November 01, 2017     Published: November 29, 2017

ABSTRACT

Lung cancer (LC) is the second common and with the highest mortality oncological disease. Specific biomarkers for its diagnostics, treatment, and prognosis are still under the investigations. Aim of our study was to evaluate the relationship between the polymorphisms of TP53 pathway genes TP53, MDM2, MDM4, the polymorphisms of HPV-associated genes MTHFR, CASP8, CCR5, and HPV infection with survival of LC patients. SNPs were genotyped using PCR-RFLP. qRT-PCR was used to detect, identify, and quantify HPV. No statistically significant differences were detected between individual SNPs and patient survival with stage I-IV LC. Cluster analysis of SNPs in genes MDM4 A/A, CCR5 wt/Δ32, MTHFR C/T, MDM2 T/T showed possible association with the worse survival. Patients who were diagnosed with C/T polymorphic variant of gene MTHFR tend not to survive stage III-IV LC (P = .12). There is a tendency between MDM2 gene T/T variant and worse survival of patients diagnosed with late stage LC (P = .11). HPV infection is very rear among LC patients (3 of 92). Overall, there is a link, although statistically insignificant, between specific SNPs and LC patient survival frequency and time, meanwhile the combination of specific SNPs showed a statistically significant measure. In conclusion, we determined statistically significant (P = .04) link between the poor survival of LC patients after surgery and the combination of polymorphic variants C/T of the MTHFR and T/T of the MDM2 genes, whereas individually these SNPs do not show significant relationship with the survival of patients after surgery.


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