We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Less common genotype variants of TP53 polymorphisms are associated with poor outcome in adult patients with adrenocortical carcinoma.
- Authors
Heinze, Britta; Herrmann, Leonie J. M.; Fassnacht, Martin; Ronchi, Cristina L.; Willenberg, Holger S.; Quinkler, Marcus; Reisch, Nicole; Zink, Martina; Allolio, Bruno; Hahner, Stefanie
- Abstract
Context: 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. Subjects and 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). Conclusion: 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.
- Subjects
P53 protein; LI-Fraumeni syndrome; GENETIC polymorphisms; GERM cells; GENETIC mutation
- Publication
European Journal of Endocrinology, 2014, Vol 170, Issue 5, p707
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-13-0788