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
Institute of Human Genetics, Polish Academy of Sciences, Ul. Strzeszyńska 32, Poznań, 60-479 Poland.
Department of Endocrinology, Metabolism and Internal Diseases, University of Medical Sciences, Poznań, Poland.
Hered Cancer Clin Pract. 2015 Mar 1;13(1):8. doi: 10.1186/s13053-015-0030-5. eCollection 2015.
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.
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.
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.
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).
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.
分化型甲状腺癌（DTC）起源于甲状腺滤泡上皮细胞，属于一组进展缓慢、预后相对较好的肿瘤。然而，复发和转移在晚期是一个严重问题。此外，高分化甲状腺癌有可能进展为侵袭性未分化癌。大多数分化型甲状腺癌是散发性的，但已知有一些增加癌症风险的等位基因。其中之一是CHEK2基因中的c.470 T＞C（p.I157T，rs17879961）错义替换。
本研究的目的是调查CHEK2基因的这种特定改变，即c.470 T＞C，是否使大波兰（Wielkopolska）人群易患甲状腺癌。
采用焦磷酸测序法对602例分化型甲状腺癌患者和829例从人群中随机选取的对照进行c.470C等位基因检测。通过卡方分布和Fisher精确检验对两组进行Hardy-Weinberg平衡（HWE）检验。使用R软件计算比值比（OR）、95%置信区间（CI）和p值。
基因分型结果显示，51例患者中存在c.470C等位基因，频率为4.49%，而在42例对照中频率为2.53%。我们证明，在大波兰人群中，c.470C CHEK2变异使分化型甲状腺癌的发病风险增加近两倍（OR = 1.81，p = 0.004）。对于c.470C等位基因纯合的女性患者，甲状腺乳头状癌的发病风险增加近13倍（OR = 12.81，p = 0.019）。
医疗保健政策制定者应考虑识别c.470C CHEK2基因变异。未来设计良好且规模更大的人群研究对于证实这些发现具有重要价值。此外，还应考虑遗传因素与环境暴露的综合作用。
