Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients.

Tzia Liang Mah,Xin Ning Adeline Yap,Ross A Soo,Srinath Sridharan,Nanpu Li,Vellaisemy Kuralmani,Sharmila Adhikari,Natalia Liem,Frank Eisenhaber,Wei Peng Yong,Vachiranee Limviphuvadh,Joo Chuan Tong,Mengling Feng,Sebastian Maurer-Stroh

doi:10.1186/1471-2164-15-s9-s20

Abstract

BackgroundNon-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide due to poor patient prognosis and clinical outcome. Here, we studied the genetic variations underlying NSCLC pathogenesis based on their association to patient outcome after gemcitabine therapy.ResultsBioinformatics analysis was used to investigate possible effects of POLA2 G583R (POLA2+1747 GG/GA, dbSNP ID: rs487989) in terms of protein function. Using biostatistics, POLA2+1747 GG/GA (rs487989, POLA2 G583R) was identified as strongly associated with mortality rate and survival time among NSCLC patients. It was also shown that POLA2+1747 GG/GA is functionally significant for protein localization via green fluorescent protein (GFP)-tagging and confocal laser scanning microscopy analysis. The single nucleotide polymorphism (SNP) causes DNA polymerase alpha subunit B to localize in the cytoplasm instead of the nucleus. This inhibits DNA replication in cancer cells and confers a protective effect in individuals with this SNP.ConclusionsThe results suggest that POLA2+1747 GG/GA may be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis.

Highlights

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide due to poor patient prognosis and clinical outcome
The results suggest that POLA2+1747 GG/GA may be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis
The results suggest that POLA2+1747 GG/ GA may be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis

Summary

Introduction

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide due to poor patient prognosis and clinical outcome. Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide with over one million deaths annually [1]. It accounts for 75% of lung cancer cases and consists of three major subtypes: adenocarcinoma, largecell carcinoma, and squamous-cell carcinoma [2]. The agent can be combined with the chemotherapy drug pemetrexed, as well as the vascular endothelial growth factor (VEGF) inhibitor, for adenocarcinoma NSCLC. Due to its significant benefit and advantageous toxicity profile, gemcitabine has since evolved to become one of the most commonly used agents for lung cancer chemotherapy

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