title: Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients.
abstract: BACKGROUND
  Non-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.
  
  
  RESULTS
  Bioinformatics 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.
  
  
  CONCLUSIONS
  The results suggest that POLA2+1747 GG/GA may be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis.
authors.forename: Tzia Liang
authors.initials: TL
authors.lastname: Mah
authors.forename: Xin Ning Adeline
authors.initials: XN
authors.lastname: Yap
authors.forename: Vachiranee
authors.initials: V
authors.lastname: Limviphuvadh
authors.forename: Nanpu
authors.initials: N
authors.lastname: Li
authors.forename: Srinath
authors.initials: S
authors.lastname: Sridharan
authors.forename: Vellaisemy
authors.initials: V
authors.lastname: Kuralmani
authors.forename: Mengling
authors.initials: M
authors.lastname: Feng
authors.forename: Natalia
authors.initials: N
authors.lastname: Liem
authors.forename: Sharmila
authors.initials: S
authors.lastname: Adhikari
authors.forename: Wei Peng
authors.initials: WP
authors.lastname: Yong
authors.forename: Ross A
authors.initials: RA
authors.lastname: Soo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maurer-Stroh
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.forename: Joo Chuan
authors.initials: JC
authors.lastname: Tong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D002467:Cell Nucleus / Q000378:metabolism; D019295:Computational Biology; D004256:DNA Polymerase I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011487:Protein Conformation; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D004256:DNA Polymerase I; D000093542:Gemcitabine