title: The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.
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.
  
  
  OBJECTIVE
  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.
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.
authors: Marta
authors: M
authors: Kaczmarek-Ryś
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Katarzyna
authors: K
authors: Ziemnicka
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.|Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland.
authors: Szymon T
authors: ST
authors: Hryhorowicz
authors: Department of Mathematical and Statistical Methods, University of Life Sciences, Poznań, Poland.
authors: Katarzyna
authors: K
authors: Górczak
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.
authors: Justyna
authors: J
authors: Hoppe-Gołębiewska
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.
authors: Marzena
authors: M
authors: Skrzypczak-Zielińska
authors: Institute for Applied Human Genetics and Oncogenetics, Zwenkau, Germany.
authors: Michalina
authors: M
authors: Tomys
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Monika
authors: M
authors: Gołąb
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Malgorzata
authors: M
authors: Szkudlarek
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Bartłomiej
authors: B
authors: Budny
authors: Department of Mathematical and Statistical Methods, University of Life Sciences, Poznań, Poland.
authors: Idzi
authors: I
authors: Siatkowski
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Paweł
authors: P
authors: Gut
authors: Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
authors: Marek
authors: M
authors: Ruchała
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.|Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland.
authors: Ryszard
authors: R
authors: Słomski
authors: Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.
authors: Andrzej
authors: A
authors: Pławski
keywords: CHEK2 gene sequence variants; Cancer risk factors; Differentiated thyroid carcinoma; Genotyping