Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

Gisella Figlioli; Bowang Chen; Rossella Elisei; Cristina Romei; Chiara Campo; Monica Cipollini; Alfonso Cristaudo; Franco Bambi; Elisa Paolicchi; Per Hoffmann; Stefan Herms; Michal Kalemba; Dorota Kula; Susana Pastor; Ricard Marcos; Antonia Velázquez; Barbara Jarzab; Stefano Landi; Kari Hemminki; Federica Gemignani; Asta Försti

doi:10.1038/srep08922

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

Gisella Figlioli, Bowang Chen, Rossella Elisei, Cristina Romei, Chiara Campo, Monica Cipollini, Alfonso Cristaudo, Franco Bambi, Elisa Paolicchi, Per Hoffmann, Stefan Herms, Michal Kalemba, Dorota Kula, Susana Pastor, Ricard Marcos, Antonia Velázquez, Barbara Jarzab, Stefano Landi, Kari Hemminki, Federica GemignaniAsta Försti

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

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.

Original language	English
Article number	8922
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep08922
Publication status	Published - 1 Jan 2015

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Figlioli, G., Chen, B., Elisei, R., Romei, C., Campo, C., Cipollini, M., Cristaudo, A., Bambi, F., Paolicchi, E., Hoffmann, P., Herms, S., Kalemba, M., Kula, D., Pastor, S., Marcos, R., Velázquez, A., Jarzab, B., Landi, S., Hemminki, K., ... Försti, A. (2015). Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk. Scientific Reports, 5, Article 8922. https://doi.org/10.1038/srep08922

@article{9e6992df92474f74856312b1c4b77ded,

title = "Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk",

abstract = "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 {\^a} '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.",

author = "Gisella Figlioli and Bowang Chen and Rossella Elisei and Cristina Romei and Chiara Campo and Monica Cipollini and Alfonso Cristaudo and Franco Bambi and Elisa Paolicchi and Per Hoffmann and Stefan Herms and Michal Kalemba and Dorota Kula and Susana Pastor and Ricard Marcos and Antonia Vel{\'a}zquez and Barbara Jarzab and Stefano Landi and Kari Hemminki and Federica Gemignani and Asta F{\"o}rsti",

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Figlioli, G, Chen, B, Elisei, R, Romei, C, Campo, C, Cipollini, M, Cristaudo, A, Bambi, F, Paolicchi, E, Hoffmann, P, Herms, S, Kalemba, M, Kula, D, Pastor, S , Marcos, R , Velázquez, A, Jarzab, B, Landi, S, Hemminki, K, Gemignani, F & Försti, A 2015, 'Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk', Scientific Reports, vol. 5, 8922. https://doi.org/10.1038/srep08922

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.

U2 - 10.1038/srep08922

DO - 10.1038/srep08922

M3 - Article

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 8922

ER -

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk

Abstract

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