Inherited variants in genes somatically mutated in thyroid cancer.

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).We per...

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Main Authors:	Chiara Campo, Aleksandra Köhler, Gisella Figlioli, Rossella Elisei, Cristina Romei, Monica Cipollini, Franco Bambi, Kari Hemminki, Federica Gemignani, Stefano Landi, Asta Försti
Format:	Article
Language:	English
Published:	Public Library of Science (PLoS)
Series:	PLoS ONE
Online Access:	http://europepmc.org/articles/PMC5391920?pdf=render

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recordtype	oai_dc
spelling	doaj-art-5c2acb27505f4b7693b787ae8ad48ff72018-08-23T04:41:22ZengPublic Library of Science (PLoS)PLoS ONE1932-6203124e017499510.1371/journal.pone.0174995Inherited variants in genes somatically mutated in thyroid cancer.Chiara CampoAleksandra KöhlerGisella FiglioliRossella EliseiCristina RomeiMonica CipolliniFranco BambiKari HemminkiFederica GemignaniStefano LandiAsta FörstiTumour 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).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.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.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.http://europepmc.org/articles/PMC5391920?pdf=render
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	Chiara Campo Aleksandra Köhler Gisella Figlioli Rossella Elisei Cristina Romei Monica Cipollini Franco Bambi Kari Hemminki Federica Gemignani Stefano Landi Asta Försti
spellingShingle	Chiara Campo Aleksandra Köhler Gisella Figlioli Rossella Elisei Cristina Romei Monica Cipollini Franco Bambi Kari Hemminki Federica Gemignani Stefano Landi Asta Försti Inherited variants in genes somatically mutated in thyroid cancer. PLoS ONE
author_facet	Chiara Campo Aleksandra Köhler Gisella Figlioli Rossella Elisei Cristina Romei Monica Cipollini Franco Bambi Kari Hemminki Federica Gemignani Stefano Landi Asta Försti
author_sort	Chiara Campo
title	Inherited variants in genes somatically mutated in thyroid cancer.
title_short	Inherited variants in genes somatically mutated in thyroid cancer.
title_full	Inherited variants in genes somatically mutated in thyroid cancer.
title_fullStr	Inherited variants in genes somatically mutated in thyroid cancer.
title_full_unstemmed	Inherited variants in genes somatically mutated in thyroid cancer.
title_sort	inherited variants in genes somatically mutated in thyroid cancer.
publisher	Public Library of Science (PLoS)
series	PLoS ONE
issn	1932-6203
description	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).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.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.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.
url	http://europepmc.org/articles/PMC5391920?pdf=render
_version_	1612675498155966464

Inherited variants in genes somatically mutated in thyroid cancer.

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