title: Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients.
abstract: OBJECTIVE
  BCL3, a known atypical IκB family member, has been documented to be upregulated in hematological malignancies and in some solid tumors, functioning as a crucial player in tumor development. Recently, rs8100239, a tag-Single Nucleotide Polymorphism (SNP) in BCL3 (T>A) has been identified, but there are no data regarding its involvement in non-small-cell lung cancer (NSCLC) initiation and progression.
  
  
  METHODS
  To study the possible association of BCL3 with NSCLC, 268 patients and 279 healthy controls were genotyped for rs8100239. Moreover, BCL3 protein expression was also investigated in 112 NSCLC cases through an immunohistochemical analysis.
  
  
  RESULTS
  NSCLC patients with AA genotype displayed significantly worse prognosis compared to T allele carriers (P<0.001), who had less frequent intermediate nuclear BCL3 expression (P=0.042). In addition, overexpression of BCL3 was detected in tumor specimens, compared to normal tissue (P<0.001). Furthermore, BCL3 protein levels were associated with five-year survival (P=0.039), maximum diameter of lesion (P=0.012), grade (P=0.002) and relapse frequency (P=0.041).
  
  
  CONCLUSIONS
  The present study is the first to show a relationship between the genetic variation rs8100239 of BCL3 and cancer patients' survival. It also represents the first quantitative evaluation of BCL3 expression in NSCLC. Our findings indicate that rs8100239 may be considered as a novel prognostic indicator, demonstrating also the overexpression of BCL3 protein in NSCLC and implicating this pivotal molecule in the pathogenesis of NSCLC.
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Foteinos-Ioannis D
authors.initials: FI
authors.lastname: Dimitrakopoulos
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Antonacopoulou
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kottorou
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Marousi
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Ioulia
authors.initials: I
authors.lastname: Koukourikou
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece.
authors.forename: Melpomeni
authors.initials: M
authors.lastname: Kalofonou
authors.affiliation: Department of Cardiothoracic Surgery, Medical School, University of Patras, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Panagopoulos
authors.affiliation: Department of Pathology, Medical School, University of Patras, Greece.
authors.forename: Chrisoula
authors.initials: C
authors.lastname: Scopa
authors.affiliation: Department of Cardiothoracic Surgery, Medical School, University of Patras, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Dougenis
authors.affiliation: Department of Anatomy, Medical School, University of Patras, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Greece. Electronic address: hkalofon@yahoo.gr.
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000081242:B-Cell Lymphoma 3 Protein; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: BCL3; Lung cancer; NF-κB; NSCLC; SNP; rs8100239