title: Less common genotype variants of TP53 polymorphisms are associated with poor outcome in adult patients with adrenocortical carcinoma.
abstract: BACKGROUND
  The Li-Fraumeni tumor syndrome is strongly associated with adrenocortical carcinoma (ACC) and is caused by germline mutations in TP53 in 70% of cases. Also, TP53 polymorphisms have been shown to influence both cancer risk and clinical outcome in several tumor entities. We, therefore, investigated TP53 polymorphisms in a cohort of adult patients with ACC.
  
  
  OBJECTIVE
  Evaluation of the role of TP53 polymorphisms in adult patients with ACC.
  
  
  METHODS
  Peripheral blood for DNA extraction was collected from 72 ACC patients. Polymorphism analysis was carried out by amplification and sequencing of exons and adjacent intron sections of TP53. Results were correlated with clinical data and the distribution of the polymorphisms was compared with published Caucasian control groups.
  
  
  RESULTS
  Compared with control groups, genotype frequencies of analyzed TP53 polymorphisms among ACC patients were significantly different in three out of four polymorphisms: IVS2+38G>C (G/G, P=0.0248), IVS3ins16 (NoIns/NoIns, P<0.0001; NoIns/Ins, P<0.0001), and IVS6+62A>G (G/G, P<0.0001; G/A, P<0.0001). Overall, the survival of ACC patients, which harbored at least one of the less frequent genotype variants of four analyzed polymorphisms (n=23), was significantly inferior (median survival: 81.0 months in patients with the common homozygous genotypes vs 20.0 months in patients with the less frequent genotypes, HR 2.56, 95% CI 1.66-7.07; P=0.001). These results were confirmed by multivariable regression analysis (HR 2.84, 95% CI 1.52-7.17; P=0.037).
  
  
  CONCLUSIONS
  Some TP53 polymorphisms seem to influence overall survival in ACC patients. This effect was observed for a combination of polymorphic changes rather than for single polymorphisms.
authors.affiliation: Endocrinology and Diabetes Unit, Department of Internal Medicine I, University Hospital of Wuerzburg, University of Wuerzburg, Oberduerrbacher Strasse 6, D-97080 Wuerzburg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Heinze
authors.forename: Leonie J M
authors.initials: LJ
authors.lastname: Herrmann
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Nicole
authors.initials: N
authors.lastname: Reisch
authors.forename: Martina
authors.initials: M
authors.lastname: Zink
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D011379:Prognosis; D012042:Registries; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53