title: CC genotype of anti-apoptotic gene BCL-2 (-938 C/A) is an independent prognostic marker of unfavorable clinical outcome in patients with non-small-cell lung cancer.
abstract: BACKGROUND
  B cell lymphoma 2 (BCL-2) gene is a well-known regulator of apoptosis and a key element in cancer development and progression. A regulatory (-938C>A, rs2279115) single-nucleotide polymorphism in the inhibitory P2 BCL-2 gene promoter generates significantly different BCL-2 promoter activities and has been associated with different clinical outcomes in various malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on the risk and survival of Indian patients suffering from NSCLC.
  
  
  METHODS
  A hospital-based case-control study of 155 age- and sex-matched patients diagnosed with NSCLC and 155 cancer-free controls was conducted and genotyped by performing PIRA-PCR to elucidate the putative association between clinical outcome and genotypes of BCL-2 (-938C>A, rs2279115). The association of the polymorphism with the survival of NSCLC patients was analyzed by Kaplan-Meier curves.
  
  
  RESULTS
  In Indian NSCLC, patients increased risk of developing NSCLC was found to be associated with BCL-2 (-938) CC genotype, [OR 3.68 (1.92-6.79), RR 1.87 (1.35-2.57) and RD 31.03 (16.79-45.27) p 0.00006 for CC and OR 2.08 (1.18-3.66), RR 1.36 (1.08-1.71) and RD 17.74 (4.68-30.81) p 0.01 for AC genotype]. Patients homozygous for C allele exhibited a significant poor overall survival compared with patients displaying AC + CC or AC or AA genotype [median survival (months) 8 vs. 11 vs. 14 vs. 35.5 (p < 0.0001)]. In addition, significant associations were observed between TNM stage, histological type, distant metastases status, family history of any cancer, gender and age group of NSCLC patients with BCL-2 (-938C>A) polymorphism.
  
  
  CONCLUSIONS
  Genetic polymorphism in the inhibitory P2 promoter region of anti-apoptotic BCL-2 genes contributes to the risk of developing non-small-cell lung cancer in Indian population. BCL-2 (-938CC) genotype was an independent adverse prognostic factor for patients with NSCLC.
authors.affiliation: Cancer Genetics Lab, Department of Biochemistry, Maulana Azad Medical College and Associated hospitals, New Delhi, India.
authors.forename: J
authors.initials: J
authors.lastname: Javid
authors.forename: R
authors.initials: R
authors.lastname: Mir
authors.forename: M
authors.initials: M
authors.lastname: Mirza
authors.forename: A
authors.initials: A
authors.lastname: Imtiyaz
authors.forename: Y
authors.initials: Y
authors.lastname: Prasant
authors.forename: Z
authors.initials: Z
authors.lastname: Mariyam
authors.forename: P K
authors.initials: PK
authors.lastname: Julka
authors.forename: A
authors.initials: A
authors.lastname: Mohan
authors.forename: M
authors.initials: M
authors.lastname: Lone
authors.forename: P C
authors.initials: PC
authors.lastname: Ray
authors.forename: A
authors.initials: A
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics