Recurrent Mutations in <i>BRCA1</i>,<i> BRCA2</i>,<i> RAD51C</i>,<i> PALB2</i> and <i>CHEK2</i> in Polish Patients with Ovarian Cancer

• Main Authors: Alicja Łukomska, Janusz Menkiszak, Jacek Gronwald, Joanna Tomiczek-Szwiec, Marek Szwiec, Marek Jasiówka, Paweł Blecharz, Tomasz Kluz, Małgorzata Stawicka-Niełacna, Radosław Mądry, Katarzyna Białkowska, Karolina Prajzendanc, Wojciech Kluźniak, Cezary Cybulski, Tadeusz Dębniak, Tomasz Huzarski, Aleksandra Tołoczko-Grabarek, Tomasz Byrski, Piotr Baszuk, Steven A. Narod, Jan Lubiński, Anna Jakubowska
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Cancers
• Subjects: ovarian cancer; recurrent mutations; <i>BRCA1</i>; <i>BRCA2</i>; <i>RAD51C</i>; <i>PALB2</i>
• Online Access: https://www.mdpi.com/2072-6694/13/4/849

The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in <i>BRCA1</i>,<i> BRCA2</i>,<i> PALB2</i>,<i> RAD51C</i>, and <i>CHEK2</i> genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in <i>BRCA1</i> (9 mutations), <i>BRCA2</i> (4 mutations), <i>RAD51C</i> (3 mutations), <i>PALB2</i> (2 mutations), and <i>CHEK2</i> (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in <i>BRCA1</i> (OR = 40.79, 95% CI: 18.67–114.78; <i>p</i> = 0.29 × 10⁻¹⁵), in <i>BRCA2</i> (OR = 25.98; 95% CI: 1.55–434.8; <i>p</i> = 0.001), in <i>RAD51C</i> (OR = 6.28; 95% CI 1.77–39.9; <i>p</i> = 0.02), and in <i>PALB2</i> (OR 3.34; 95% CI: 1.06–14.68; <i>p</i> = 0.06). There was no association found for <i>CHEK2.</i> We found that pathogenic mutations in <i>BRCA1</i>,<i> BRCA2</i>,<i> RAD51C</i> or <i>PALB2</i> are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.