Gąsior-Perczak Danuta, Kowalik Artur, Gruszczyński Krzysztof, Walczyk Agnieszka, Siołek Monika, Pałyga Iwona, Trepka Sławomir, Mikina Estera, Trybek Tomasz, Kopczyński Janusz, Suligowska Agnieszka, Ślusarczyk Rafał, Gonet Agnieszka, Jaskulski Jarosław, Orłowski Paweł, Chrapek Magdalena, Góźdź Stanisław, Kowalska Aldona
Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland.
Endocrinology Clinic, Holycross Cancer Center, Artwińskiego 3, 25-734 Kielce, Poland.
Cancers (Basel). 2021 Jan 26;13(3):470. doi: 10.3390/cancers13030470.
The gene is involved in the repair of damaged DNA. germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. mutations were found in 240 (15.5%) of patients. A I157T missense mutation was found in 12.3%, and truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women ( = 0.038), and were associated with vascular invasion (OR, 6.91; < 0.0001) and intermediate or high initial risk (OR, 1.92; = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.
该基因参与受损DNA的修复。种系突变会损害这种修复机制，导致基因组不稳定，并增加包括甲状腺乳头状癌（PTC）在内的各种癌症的风险。在此，我们探讨种系突变是否预示PTC的临床病程更差。该研究纳入了在单一中心接受治疗的1547例未经选择的PTC患者（1358例女性和189例男性）。评估了突变状态与临床病理特征、治疗反应和疾病转归之间的关系。在240例（15.5%）患者中发现了突变。发现12.3%的患者存在I157T错义突变，2.8%的患者存在截短突变（IVS2 + 1G > A、del5395、1100delC）。截短突变在女性中更常见（P = 0.038），在多因素分析中与血管侵犯（比值比，6.91；P < 0.0001）以及中度或高度初始风险（比值比，1.92；P = 0.0481）相关。在存在I157T错义突变的患者中，这些参数未观察到显著差异。总之，截短突变与血管侵犯以及复发/持续存在的中度和高度初始风险相关。截短突变和错义突变均与疾病的初始治疗反应和转归较差无关。
