Akt1 genetic variants confer increased susceptibility to thyroid cancer

in Endocrine Connections
View More View Less
  • 1 T Crezee, Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands
  • 2 M Petrulea, Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, , Cluj-Napoca, Romania
  • 3 D Piciu, Department of Oncology, Oncology Institute, Cluj-Napoca, Romania
  • 4 M Jaeger, Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands
  • 5 J Smit, Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands
  • 6 T Plantinga, Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands
  • 7 C Georgescu, Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, Cluj-Napoca, Romania
  • 8 R Netea-Maier, Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands

Correspondence: Romana Netea-Maier, Email: romana.netea-maier@radboudumc.nl

The PI3K-Akt-mTOR pathway plays a central role in the development of non-medullary thyroid carcinoma (NMTC). Although somatic mutations have been identified in these genes in NMTC patients, the role of germline variants has not been investigated. Here, we selected frequently occurring genetic variants in AKT1, AKT2, AKT3, PIK3CA and MTOR and have assessed their effect on NMTC susceptibility, progression and clinical outcome in a Dutch discovery cohort (154 patients, 188 controls) and a Romanian validation cohort (159 patients, 260 controls). Significant associations with NMTC susceptibility were observed for AKT1 polymorphisms rs3803304, rs2494732 and rs2498804 in the Dutch discovery cohort, of which the AKT1 rs3803304 association was confirmed in the Romanian validation cohort. No associations were observed between PI3K-Akt-mTOR polymorphisms and clinical parameters including histology, TNM staging, treatment response and clinical outcome. Functionally, cells bearing the associated AKT1 rs3803304 risk allele exhibit increased levels of phosphorylated Akt protein, potentially leading to elevated signaling activity of the oncogenic Akt pathway. All together, germline encoded polymorphisms in the PI3K-Akt-mTOR pathway could represent important risk factors in development of NMTC.

If the inline PDF is not rendering correctly, you can download the PDF file here.

 

     European Society of Endocrinology

     Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 52 52 52
PDF Downloads 43 43 43