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Novel Genome-Wide Association Study-Based Candidate Loci for Differentiated Thyroid Cancer Risk

Figlioli, Gisella; Koehler, Aleksandra; Chen, Bowang; Elisei, Rossella; Romei, Cristina; Cipollini, Monica; Cristaudo, Alfonso; Bambi, Franco; Paolicchi, Elisa and Hoffmann, Per, et al. (2014) In Journal of Clinical Endocrinology and Metabolism 99(10). p.2084-2092
Abstract
Context: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3). Our recently published GWAS suggested additional susceptibility loci specific for the high-incidence Italian population. Objective: The purpose of this study was to identify novel Italian-specific DTC risk variants based on our GWAS and to test them further in low-incidence populations. Design: We investigated 45 SNPs selected from our GWAS first in an Italian population. SNPs that showed suggestive evidence of association were investigated in the Polish and Spanish cohorts. Results: The combined analysis of the GWAS... (More)
Context: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3). Our recently published GWAS suggested additional susceptibility loci specific for the high-incidence Italian population. Objective: The purpose of this study was to identify novel Italian-specific DTC risk variants based on our GWAS and to test them further in low-incidence populations. Design: We investigated 45 SNPs selected from our GWAS first in an Italian population. SNPs that showed suggestive evidence of association were investigated in the Polish and Spanish cohorts. Results: The combined analysis of the GWAS and the Italian replication study (2260 case patients and 2218 control subjects) provided strong evidence of association with rs10136427 near BATF (odds ratio [ OR] = 1.40, P = 4.35 x 10(-7)) and rs7267944 near DHX35 (OR = 1.39, P = 2.13 x 10(-8)). A possible role in DTC susceptibility in the Italian populations was also found for rs13184587 (ARSB) (P = 8.54 x 10(-6)) and rs1220597 (SPATA13) (P = 3.25 x 10(-6)). Only the associations between rs10136427 and rs7267944 and DTC risk were replicated in the Polish and the Spanish populations with little evidence of population heterogeneity (GWAS and all replications combined, OR = 1.30, P = 9.30 x 10(-7) and OR = 1.32, P = 1.34 x 10(-8), respectively). In silico analyses provided new insights into the possible functional consequences of the SNPs that showed the strongest association with DTC. Conclusions: Our findings provide evidence for novel DTC susceptibility variants. Further studies are warranted to identify the specific genetic variants responsible for the observed associations and to functionally validate our in silico predictions. (Less)
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Contribution to journal
publication status
published
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Journal of Clinical Endocrinology and Metabolism
volume
99
issue
10
pages
2084 - 2092
publisher
The Endocrine Society
external identifiers
  • wos:000343423300034
  • scopus:84907662220
ISSN
1945-7197
DOI
10.1210/jc.2014-1734
language
English
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yes
id
977f3c26-3bc6-4546-891c-4b18dc298e44 (old id 4787437)
date added to LUP
2014-12-01 07:36:10
date last changed
2017-10-08 03:54:35
@article{977f3c26-3bc6-4546-891c-4b18dc298e44,
  abstract     = {Context: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3). Our recently published GWAS suggested additional susceptibility loci specific for the high-incidence Italian population. Objective: The purpose of this study was to identify novel Italian-specific DTC risk variants based on our GWAS and to test them further in low-incidence populations. Design: We investigated 45 SNPs selected from our GWAS first in an Italian population. SNPs that showed suggestive evidence of association were investigated in the Polish and Spanish cohorts. Results: The combined analysis of the GWAS and the Italian replication study (2260 case patients and 2218 control subjects) provided strong evidence of association with rs10136427 near BATF (odds ratio [ OR] = 1.40, P = 4.35 x 10(-7)) and rs7267944 near DHX35 (OR = 1.39, P = 2.13 x 10(-8)). A possible role in DTC susceptibility in the Italian populations was also found for rs13184587 (ARSB) (P = 8.54 x 10(-6)) and rs1220597 (SPATA13) (P = 3.25 x 10(-6)). Only the associations between rs10136427 and rs7267944 and DTC risk were replicated in the Polish and the Spanish populations with little evidence of population heterogeneity (GWAS and all replications combined, OR = 1.30, P = 9.30 x 10(-7) and OR = 1.32, P = 1.34 x 10(-8), respectively). In silico analyses provided new insights into the possible functional consequences of the SNPs that showed the strongest association with DTC. Conclusions: Our findings provide evidence for novel DTC susceptibility variants. Further studies are warranted to identify the specific genetic variants responsible for the observed associations and to functionally validate our in silico predictions.},
  author       = {Figlioli, Gisella and Koehler, Aleksandra and Chen, Bowang and Elisei, Rossella and Romei, Cristina and Cipollini, Monica and Cristaudo, Alfonso and Bambi, Franco and Paolicchi, Elisa and Hoffmann, Per and Herms, Stefan and Kalemba, Michal and Kula, Dorota and Pastor, Susana and Marcos, Ricard and Velazquez, Antonia and Jarzab, Barbara and Landi, Stefano and Hemminki, Kari and Försti, Asta and Gemignani, Federica},
  issn         = {1945-7197},
  language     = {eng},
  number       = {10},
  pages        = {2084--2092},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Novel Genome-Wide Association Study-Based Candidate Loci for Differentiated Thyroid Cancer Risk},
  url          = {http://dx.doi.org/10.1210/jc.2014-1734},
  volume       = {99},
  year         = {2014},
}