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Inherited variants in genes somatically mutated in thyroid cancer

Campo, Chiara ; Kohler, Aleksandra ; Figlioli, Gisella ; Elisei, Rossella ; Romei, Cristina ; Cipollini, Monica ; Bambi, Franco ; Hemminki, Kari LU ; Gemignani, Federica and Landi, Stefano , et al. (2017) In PLoS ONE 12(4).
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
12
issue
4
article number
e0174995
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85017469092
  • pmid:28410400
  • wos:000399955600010
ISSN
1932-6203
DOI
10.1371/journal.pone.0174995
language
English
LU publication?
yes
id
48d4e396-36ae-42cb-b0d6-243803b17372
date added to LUP
2017-05-23 10:10:06
date last changed
2024-02-29 15:30:44
@article{48d4e396-36ae-42cb-b0d6-243803b17372,
  abstract     = {{<p>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.</p>}},
  author       = {{Campo, Chiara and Kohler, Aleksandra and Figlioli, Gisella and Elisei, Rossella and Romei, Cristina and Cipollini, Monica and Bambi, Franco and Hemminki, Kari and Gemignani, Federica and Landi, Stefano and Forsti, Asta}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Inherited variants in genes somatically mutated in thyroid cancer}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0174995}},
  doi          = {{10.1371/journal.pone.0174995}},
  volume       = {{12}},
  year         = {{2017}},
}