Koczkowska Magdalena, Krawczynska Natalia, Stukan Maciej, Kuzniacka Alina, Brozek Izabela, Sniadecki Marcin, Debniak Jaroslaw, Wydra Dariusz, Biernat Wojciech, Kozlowski Piotr, Limon Janusz, Wasag Bartosz, Ratajska Magdalena
Department of Biology and Medical Genetics, Medical University of Gdansk, Debinki 1 St., 80-210 Gdansk, Poland.
Laboratory of Clinical Genetics, University Clinical Centre, Smoluchowskiego 17 St., 80-952 Gdansk, Poland.
Cancers (Basel). 2018 Nov 14;10(11):442. doi: 10.3390/cancers10110442.
Constitutional loss-of-function pathogenic variants in the tumor suppressor genes and are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs74) and c.3700_3704del (p.Val1234Glnfs8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with and reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in , 1/333 in , 2/333 in , 1/333 in , 1/333 in , 2/333 in , 1/333 in and 1/333 in , accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals.
肿瘤抑制基因中的胚系功能丧失性致病变异与卵巢癌（OC）风险升高广泛相关。由于只有约15%的OC患者携带该致病变异，因此鉴定其他潜在的OC易感基因具有重要的临床意义。在此，我们在波兰一个由333例未经选择的OC病例组成的大群体中，确定了该基因以及其他与癌症相关的23个基因中胚系致病变异的流行情况和谱型。约21%的病例（71/333）携带该致病或可能致病的变异，其中c.5266dup（p.Gln1756Profs74）和c.3700_3704del（p.Val1234Glnfs8）最为常见。此外，约6%的女性（20/333）是其他癌症相关基因中致病或可能致病变异的携带者，其中报告的 和 是最常发生突变的，分别占病例的1.8%（6/333）和1.2%（4/333）。我们还在其他基因中发现了10个致病或可能致病的变异： 中1/333、 中1/333、 中2/333、 中1/333、 中1/333、 中2/333、 中1/333和 中1/333，占中低外显率基因中所有检测到变异的50%。我们的研究结果证实了波兰人群中存在其他与OC相关的基因，这可能会改善这些个体的个性化风险评估。
