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The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population

BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a w...

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Autores principales: Kaczmarek-Ryś, Marta, Ziemnicka, Katarzyna, Hryhorowicz, Szymon T, Górczak, Katarzyna, Hoppe-Gołębiewska, Justyna, Skrzypczak-Zielińska, Marzena, Tomys, Michalina, Gołąb, Monika, Szkudlarek, Malgorzata, Budny, Bartłomiej, Siatkowski, Idzi, Gut, Paweł, Ruchała, Marek, Słomski, Ryszard, Pławski, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367841/
https://www.ncbi.nlm.nih.gov/pubmed/25798211
http://dx.doi.org/10.1186/s13053-015-0030-5
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author Kaczmarek-Ryś, Marta
Ziemnicka, Katarzyna
Hryhorowicz, Szymon T
Górczak, Katarzyna
Hoppe-Gołębiewska, Justyna
Skrzypczak-Zielińska, Marzena
Tomys, Michalina
Gołąb, Monika
Szkudlarek, Malgorzata
Budny, Bartłomiej
Siatkowski, Idzi
Gut, Paweł
Ruchała, Marek
Słomski, Ryszard
Pławski, Andrzej
author_facet Kaczmarek-Ryś, Marta
Ziemnicka, Katarzyna
Hryhorowicz, Szymon T
Górczak, Katarzyna
Hoppe-Gołębiewska, Justyna
Skrzypczak-Zielińska, Marzena
Tomys, Michalina
Gołąb, Monika
Szkudlarek, Malgorzata
Budny, Bartłomiej
Siatkowski, Idzi
Gut, Paweł
Ruchała, Marek
Słomski, Ryszard
Pławski, Andrzej
author_sort Kaczmarek-Ryś, Marta
collection PubMed
description BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. AIM OF THE STUDY: The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. METHODS: 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher’s exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. RESULTS: The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). CONCLUSIONS: Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13053-015-0030-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-43678412015-03-21 The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population Kaczmarek-Ryś, Marta Ziemnicka, Katarzyna Hryhorowicz, Szymon T Górczak, Katarzyna Hoppe-Gołębiewska, Justyna Skrzypczak-Zielińska, Marzena Tomys, Michalina Gołąb, Monika Szkudlarek, Malgorzata Budny, Bartłomiej Siatkowski, Idzi Gut, Paweł Ruchała, Marek Słomski, Ryszard Pławski, Andrzej Hered Cancer Clin Pract Research BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. AIM OF THE STUDY: The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. METHODS: 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher’s exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. RESULTS: The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). CONCLUSIONS: Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13053-015-0030-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-01 /pmc/articles/PMC4367841/ /pubmed/25798211 http://dx.doi.org/10.1186/s13053-015-0030-5 Text en © Kaczmarek-Rys et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kaczmarek-Ryś, Marta
Ziemnicka, Katarzyna
Hryhorowicz, Szymon T
Górczak, Katarzyna
Hoppe-Gołębiewska, Justyna
Skrzypczak-Zielińska, Marzena
Tomys, Michalina
Gołąb, Monika
Szkudlarek, Malgorzata
Budny, Bartłomiej
Siatkowski, Idzi
Gut, Paweł
Ruchała, Marek
Słomski, Ryszard
Pławski, Andrzej
The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title_full The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title_fullStr The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title_full_unstemmed The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title_short The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
title_sort c.470 t > c chek2 missense variant increases the risk of differentiated thyroid carcinoma in the great poland population
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367841/
https://www.ncbi.nlm.nih.gov/pubmed/25798211
http://dx.doi.org/10.1186/s13053-015-0030-5
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