Feszak Sylwia, Kluźniak Wojciech, Feszak Igor, Chady Magdalena, Wokołorczyk Dominika, Stempa Klaudia, Rudnicka Helena, Gliniewicz Katarzyna, Jakubowska Anna, Lener Marcin, Czepukowicz Maciej, Huzarski Tomasz, Dębniak Tadeusz, Gronwald Jacek, Lubiński Jan, Cybulski Cezary
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, 71-252, Poland.
Department of Pediatrics, Pediatric Oncology, and Immunology, Pomeranian Medical University, Szczecin, 71-252, Poland.
Hered Cancer Clin Pract. 2025 Aug 6;23(1):19. doi: 10.1186/s13053-025-00320-z.
The genetic background of ductal carcinoma in situ (DCIS) has not been well explored. Previously, we reported that Polish founder mutations of confer susceptibility to DCIS. The aim of our study was to investigate the role of , , and mutations in the ethology of DCIS.
We studied 564 Polish women with DCIS for eight Polish founder alleles, including four in (c.1100delC, c.444 + 1G > A, del5395 and c.470T > C), two in (c.509_510delGA and c.172_175delTTGT), one in (c.657_661delACAAA) and one in (c.1667_1667 + 3delAGTA). To investigate the association of these alleles with DCIS risk, we used mutation frequencies in cancer-free controls as a reference (4000 to 4702 controls for different variants). To analyze survival, patients were followed on average for 156 months.
A mutation (all variants combined) was associated with an increased risk of DCIS (OR = 1.7, = 0.003). The risk was higher for truncating mutations (OR = 3.0, = 0.001) than for a missense variant c.470T > C (OR = 1.5, = 0.04). The risk was highest for carriers of truncating mutations with a family history of breast cancer (OR = 4.2, = 0.01). There were no deaths reported in 52 mutation carriers during the follow up time. , and mutations were rare among cases and were not associated with DCIS risk in Polish women.
Based on the current study, women with a mutation face an increased risk of DCIS. The presence of DCIS should be considered during surveillance of mutation carriers. On the other hand, DCIS patients should receive genetic counseling and testing for mutations.
导管原位癌（DCIS）的遗传背景尚未得到充分研究。此前，我们报道波兰的始祖突变赋予了患DCIS的易感性。本研究的目的是调查 、 、 和 突变在DCIS病因学中的作用。
我们研究了564名患有DCIS的波兰女性，检测了8个波兰始祖等位基因，其中 有4个（c.1100delC、c.444+1G>A、del5395和c.470T>C）， 有2个（c.509_510delGA和c.172_175delTTGT）， 有1个（c.657_661delACAAA）， 有1个（c.1667_1667+3delAGTA）。为了研究这些等位基因与DCIS风险的关联，我们将无癌对照中的突变频率作为参考（不同变体的对照为4000至4702人）。为了分析生存率，对患者平均随访156个月。
突变（所有变体合并）与DCIS风险增加相关（OR=1.7， =0.003）。 截短突变的风险（OR=3.0， =0.001）高于错义变体c.470T>C（OR=1.5， =0.04）。有乳腺癌家族史的 截短突变携带者风险最高（OR=4.2， =0.01）。在随访期间，52名 突变携带者中未报告死亡病例。 、 和 突变在病例中很少见，与波兰女性的DCIS风险无关。
基于目前的研究，携带 突变的女性患DCIS的风险增加。在对 突变携带者进行监测时应考虑DCIS的存在。另一方面，DCIS患者应接受 突变的遗传咨询和检测。
