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Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer.

ABSTRACT: Ovarian cancer is one of the most common types of cancer in women. The repair system via homologous recombination repairs double-strand breaks (DSB) of DNA, which are the most mortal for cell, out of all DNA damages. The genes, which encode the double-strand break repairing proteins, are highly polymorphic and, taking into account the significance of the repaired defects for cancer development, it seems important to learn the role of the polymorphisms in ovarian cancer development. The aim of the study was to determine the relationship between DNA repair genes via homologous recombination (HR) and modulation of the risk of ovarian cancer. The following polymorphisms were analysed: XRCC3-Thr241Met (rs861539), XRCC2--41657C/T (rs718282), XRCC2-Arg188His (rs3218536), BRCA1-Q356R (rs1799950) and RAD51-135 G/C (rs1801320). The study group included 600 patients with ovarian cancer and 600 healthy controls. The PCR-RFLP (PCR-based restriction fragment length polymorphism) technique was applied for polymorphism analysis. Allele XRCC3-241Met (OR 0.85, 95%CI 0.72-0.99, p

SUBMITTER: Smolarz B

PROVIDER: S-EPMC6815278 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer.

Smolarz Beata B Michalska Magdalena M MM Samulak Dariusz D Romanowicz Hanna H Wójcik Luiza L

Pathology oncology research : POR 20190202 4

Ovarian cancer is one of the most common types of cancer in women. The repair system via homologous recombination repairs double-strand breaks (DSB) of DNA, which are the most mortal for cell, out of all DNA damages. The genes, which encode the double-strand break repairing proteins, are highly polymorphic and, taking into account the significance of the repaired defects for cancer development, it seems important to learn the role of the polymorphisms in ovarian cancer development. The aim of th ...[more]

PMID: 30712190

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Project description:ObjectiveThe status of homologous recombination repair (HRR) gene mutations and their impact on the survival of patients with Chinese epithelial ovarian cancer (EOC) are still unclear. In this study, we retrospectively analyzed the mutations of HRR genes in tumor tissues and evaluated their values for predicting the survival of Chinese EOC patients.MethodsA total of 273 primary EOC patients from five different hospitals between 2015 and 2016 were recruited. All patients received staging surgeries or debulking surgeries combined with systemic platinum-based chemotherapy. DNA was extracted from formalin-fixed, paraffin-embedded sections and analyzed for mutations using a 21-gene panel (including 13 well-known HRR genes) by next-generation sequencing.ResultsHigh-grade serous carcinoma (HGSOC) accounted for 76.2% of the cohort. A total of 34.1% (93/273) cases had 99 deleterious mutations in 9 HRR genes, namely, BRCA1 (56/273, 20.5%), BRCA2 (20/273, 7.3%), ATM (5/273, 1.8%), RAD51C (5/273, 1.8%), RAD51D (5/273, 1.8%), BRIP1 (2/273, 1.8%), CHEK2 (2/273, 0.7%), FANCI (2/273, 0.7%), and RAD54L (1/273, 0.4%). There is a strong mutual exclusion between HRR genes. The mutation landscape revealed several unappreciated deleterious variants in BRCA1/2 and other HRR genes reported previously. Estimated according to the mutation allele frequency, about 4.8% of the patients had potential somatic HRR gene mutations, which might be underestimated. Moreover, HRR mutations mainly exist in HGSOC (83/208, 39.9%), clear cell (2/30, 6.7%), and endometroid subtypes (8/20, 40%), but not seen in other rare subtypes. BRCA1 mutations tend to be present in younger patients with family history or multiple primary foci. Patients with BRCA1/2 mutations tend to have a longer progression-free survival and overall survival, while other HRR mutation carriers tend to have a shorter progression-free survival, but no significant difference in overall survival.ConclusionThis study revealed the distribution of HRR gene mutations in Chinese EOC tissues. BRCA1/2 account for the majority of HRR gene mutations and predict long prognosis in HGSOC. Non-BRCA HRR mutations also account for a very important proportion and might be associated with poor prognosis in HGSOC. It is suggested that HRR gene mutations need to be detected in EOC tissues and germline status be further clarified in clinical algorithm for potential targeted therapy, genetic screening, and prognosis prediction.

Dataset Information

Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer.

Publications

Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer.

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