title: BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients.
abstract: OBJECTIVE
  Malignant pleural mesothelioma is an incurable, asbestos-associated cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis deregulation is an important feature of cancer and survivin, a member of the inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been suggested to have a role in the development and progression of several cancers. Genetic variability, in particular single nucleotide polymorphisms in the BIRC5 promoter, may affect the protein's expression levels. The aim of our study was to elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on survivin expression, patient survival and age at diagnosis in malignant pleural mesothelioma.
  
  
  METHODS
  Archival mesothelioma samples from 101 Slovenian patients were immunohistochemically analysed for survivin expression. DNA was extracted from tumour samples and genotyped for three BIRC5 promoter single nucleotide polymorphisms (-31G > C, -241C > T and -625G > C). Genotypes were associated with nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes, histological type, gender and asbestos exposure were included in univariate Cox survival analyses.
  
  
  RESULTS
  Survivin expression was detected in both tumour cell nuclei and cytoplasms in all analysed samples. No association between BIRC5 promoter polymorphism genotypes or haplotypes and nuclear survivin expression was found. Polymorphism -241C > T affected patients' age at diagnosis. Survival analysis confirmed that younger age at diagnosis and epitheloid histological type improved survival, but no significant effects of nuclear survivin expression or genotype/haplotype on overall survival were observed.
  
  
  CONCLUSIONS
  Our findings indicate no relationship between BIRC5 genotypes and survivin expression or overall survival in mesothelioma patients. We observed that BIRC5 -241C > T polymorphism had a significant effect on patient age at diagnosis.
authors.affiliation: College of Health Care Izola, University of Primorska, Polje 42, 6310 Izola, Slovenia. julija.hmeljak@vszi.upr.si
authors.forename: Julija
authors.initials: J
authors.lastname: Hmeljak
authors.forename: Nina
authors.initials: N
authors.lastname: Erčulj
authors.forename: Vita
authors.initials: V
authors.lastname: Dolžan
authors.forename: Izidor
authors.initials: I
authors.lastname: Kern
authors.forename: Andrej
authors.initials: A
authors.lastname: Cör
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010997:Pleural Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin