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Hereditary Cancer in Clinical Practice
Published in: Hereditary Cancer in Clinical Practice 1/2015

Open Access 01-12-2015 | Research

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

Authors: Marta Kaczmarek-Ryś, Katarzyna Ziemnicka, Szymon T Hryhorowicz, Katarzyna Górczak, Justyna Hoppe-Gołębiewska, Marzena Skrzypczak-Zielińska, Michalina Tomys, Monika Gołąb, Malgorzata Szkudlarek, Bartłomiej Budny, Idzi Siatkowski, Paweł Gut, Marek Ruchała, Ryszard Słomski, Andrzej Pławski

Published in: Hereditary Cancer in Clinical Practice | Issue 1/2015

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Abstract

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.
Appendix
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Metadata
Title
The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population
Authors
Marta Kaczmarek-Ryś
Katarzyna Ziemnicka
Szymon T Hryhorowicz
Katarzyna Górczak
Justyna Hoppe-Gołębiewska
Marzena Skrzypczak-Zielińska
Michalina Tomys
Monika Gołąb
Malgorzata Szkudlarek
Bartłomiej Budny
Idzi Siatkowski
Paweł Gut
Marek Ruchała
Ryszard Słomski
Andrzej Pławski
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Hereditary Cancer in Clinical Practice / Issue 1/2015
Electronic ISSN: 1897-4287
DOI
https://doi.org/10.1186/s13053-015-0030-5

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