Inherited variants in genes somatically mutated in thyroid cancer

Research output: Contribution to journalArticle

Abstract

Background Tumour suppressor genes when mutated in the germline cause various cancers, but they can also be somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic well-differentiated thyroid cancer (WDTC). Methods We performed a two-stage case-control association study with a total of 2214 cases and 2108 healthy controls from an Italian population. By genotyping 34 single nucleotide polymorphisms (SNPs), we covered a total of 59 missense SNPs and SNPs located in the 5' and 3' untranslated regions (UTRs) of 10 different genes. Results The Italian1 series showed a suggestive association for 8 SNPs, from which three were replicated in the Italian2 series. The meta-analysis revealed a study-wide significant association for rs459552 (OR: 0.84, 95%CI: 0.75-0.94) and rs1800900 (OR: 1.15, 95%CI: 1.05-1.27), located in the APC and GNAS genes, respectively. The APC rs459552 is a missense SNP, located in a conserved amino acid position, but without any functional consequences. The GNAS rs1800900 is located at a conserved 5'UTR and according to the experimental ENCODE data it may affect promoter and histone marks in different cell types. Conclusions The results of this study yield new insights on WDTC, showing that inherited variants in the APC and GNAS genes can play a role in the etiology of thyroid cancer. Further studies are necessary to better understand the role of the identified SNPs in the development of WDTC and to functionally validate our in silico predictions.

Details

Authors
  • Chiara Campo
  • Aleksandra Kohler
  • Gisella Figlioli
  • Rossella Elisei
  • Cristina Romei
  • Monica Cipollini
  • Franco Bambi
  • Kari Hemminki
  • Federica Gemignani
  • Stefano Landi
  • Asta Forsti
Organisations
External organisations
  • University of Pisa
  • Meyer Children's Hospital
  • German Cancer Research Centre
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Article numbere0174995
JournalPLoS ONE
Volume12
Issue number4
Publication statusPublished - 2017 Apr 1
Publication categoryResearch
Peer-reviewedYes