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- Title
The missense variant increases c.470 T > C CHEK2 the risk of differentiated thyroid carcinoma in the Great Poland population.
- Authors
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
- 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.
- Subjects
WIELKOPOLSKA (Poland); MISSENSE mutation; EPITHELIAL cells; THYROID cancer; CANCER relapse; PROGNOSIS; CANCER risk factors
- Publication
Hereditary Cancer in Clinical Practice, 2015, Vol 13, Issue 1, p1
- ISSN
1731-2302
- Publication type
Article
- DOI
10.1186/s13053-015-0030-5