Cieszyńska Monika, Kluźniak Wojciech, Wokołorczyk Dominika, Cybulski Cezary, Huzarski Tomasz, Gronwald Jacek, Falco Michał, Dębniak Tadeusz, Jakubowska Anna, Derkacz Róża, Marciniak Wojciech, Lener Marcin, Woronko Karolina, Mocarz Dominika, Baszuk Piotr, Bryśkiewicz Marta, Narod Steven A, Lubiński Jan
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 71-252 Szczecin, Poland.
Department of Clinical Genetics and Pathology, University of Zielona Góra, 65-417 Zielona Góra, Poland.
Cancers (Basel). 2022 Feb 15;14(4):957. doi: 10.3390/cancers14040957.
The goal of this study was to estimate the risk of thyroid cancer following breast cancer and to identify therapeutic and genetic risk factors for the development of thyroid cancer after breast cancer. We followed 10,832 breast cancer patients for a mean of 14 years for new cases of thyroid cancer. All women were genotyped for three Polish founder mutations in BRCA1 (C61G, 4153delA, 5382insC) and four mutations in CHEK2 (1100delC, IVS2 + 1G/A, del5395, I157T). Information was collected on chemotherapy, radiotherapy, hormonal therapies, and oophorectomy. Of the 10,832 women, 53 (0.49%) developed a second primary thyroid cancer. Based on Polish population statistics, the expected number was 12.4 (SIR = 4.3). The ten-year risk of developing thyroid cancer was higher in women who carried a CHEK2 mutation (1.5%) than in women who carried no mutation (0.9%). The age-adjusted hazard ratio for developing thyroid cancer was 1.89 (0.46-7.79; = 0.38) for those with a CHEK2 protein-truncating mutation and 2.75 (1.29-5.85; = 0.009) for those with a CHEK2 missense mutation.
本研究的目的是评估乳腺癌后发生甲状腺癌的风险，并确定乳腺癌后发生甲状腺癌的治疗和遗传风险因素。我们对10832名乳腺癌患者进行了平均14年的随访，以观察甲状腺癌新发病例。所有女性均针对BRCA1基因的三种波兰始祖突变（C61G、4153delA、5382insC）和CHEK2基因的四种突变（1100delC、IVS2 + 1G/A、del5395、I157T）进行了基因分型。收集了关于化疗、放疗、激素治疗和卵巢切除术的信息。在这10832名女性中，有53人（0.49%）发生了第二原发性甲状腺癌。根据波兰人口统计数据，预期病例数为12.4例（标准化发病比[SIR]=4.3）。携带CHEK2突变的女性发生甲状腺癌的十年风险（1.5%）高于未携带突变的女性（0.9%）。对于携带CHEK2蛋白截短突变的患者，发生甲状腺癌的年龄调整风险比为1.89（0.46 - 7.79；P = 0.38），对于携带CHEK2错义突变的患者，该风险比为2.75（1.29 - 5.85；P = 0.009）。
