TY - JOUR
T1 - Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk
AU - Figlioli, Gisella
AU - Chen, Bowang
AU - Elisei, Rossella
AU - Romei, Cristina
AU - Campo, Chiara
AU - Cipollini, Monica
AU - Cristaudo, Alfonso
AU - Bambi, Franco
AU - Paolicchi, Elisa
AU - Hoffmann, Per
AU - Herms, Stefan
AU - Kalemba, Michal
AU - Kula, Dorota
AU - Pastor, Susana
AU - Marcos, Ricard
AU - Velázquez, Antonia
AU - Jarzab, Barbara
AU - Landi, Stefano
AU - Hemminki, Kari
AU - Gemignani, Federica
AU - Försti, Asta
PY - 2015/1/1
Y1 - 2015/1/1
N2 - A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR = 1.36, 95%CI 1.20-1.53, p-value = 7.41 × 10-7) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16-1.44, p-value = 4.42 × 10-6). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend = 3.13 × 10 â '47). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.
AB - A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR = 1.36, 95%CI 1.20-1.53, p-value = 7.41 × 10-7) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16-1.44, p-value = 4.42 × 10-6). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend = 3.13 × 10 â '47). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.
UR - https://www.scopus.com/pages/publications/84924390024
U2 - 10.1038/srep08922
DO - 10.1038/srep08922
M3 - Article
SN - 2045-2322
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 8922
ER -
