ArticleJournal of ovarian research2025
Mutational landscape and risk estimates of DDR genes in Chinese ovarian cancer patients.
Article in Journal of ovarian research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPathogenic/likely pathogenic variants (P/LPVs) in DNA damage response (DDR) genes are known ovarian cancer (OC) risk factors, but gene-specific risk estimates in Han Chinese remain unclear.
objectiveTo accurately assess the risk associated with DDR genes in the Han Chinese population to facilitate personalized risk management and enhance clinical decision-making.
methodsWe performed next-generation sequencing of 45 DDR genes in 666 OC patients from Henan, China. Associations between P/LPVs and clinical features were assessed using chi-squared tests. Variant frequencies were compared with population controls (gnomAD and ChinaMAP databases) to estimate gene-specific odds ratios (ORs) using Fisher’s test.
resultsIn Henan Ovarian Cancer patients, the median disease onset age was 53 years (range: 24–81), with 7.7% diagnosed before 40. Most patients had advanced disease (56.5% Stage III, 18.9% Stage IV), and 75.8% had high-grade serous carcinoma (HGSC). P/LPVs in BRCA1/2 were significantly associated with the HGSC subtype and a positive family history (p < 0.001 for both). Beyond BRCA1 (OR = 125.5/146.1) and BRCA2 (OR = 17.9/20.2), significantly elevated ovarian cancer risks were observed for RAD51D, RAD51C, and MSH2 (OR: 10.1–35.4, all p < 0.05).
conclusionsThis study provides the first gene-specific ovarian cancer risk estimates for DDR genes in Han Chinese, expanding the high-risk gene spectrum. By defining population-specific risk magnitudes, our findings provide a framework for clinical risk stratification, and underscore the need to tailor screening and prevention strategies to China’s distinct genetic landscape.
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