ArticleBMC cancer2025
Clinicopathological features of Chinese ovarian cancer patients with double heterozygosity for cancer-predisposed genes.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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11 authors.
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Abstract
backgroundDouble heterozygosity (DH) is rarely reported in hereditary ovarian cancer. The clinicopathological and pedigree features of ovarian cancer patients harboring DH of cancer-predisposed genes are not well established.
methodsThis study included ovarian cancer patients who received genetic counseling at Peking University Third Hospital between 2018 and 2024. Among patients who received genetic testing, 75 patients were found to carry germline pathogenic variants (PVs) in BRCA1. In 75 BRCA1 PV carriers, 6 unrelated patients harboring additional germline PV in cancer-predisposed genes were identified. The clinicopathological characteristics and family history of the 75 ovarian cancer patients were collected.
resultsSix patients harboring germline BRCA1 variant and a concurrent germline variant in cancer-predisposed genes were identified. Coupling with BRCA1 PV, the additional variant involved MUTYH/RECQL4, RAD51C, RECQL4, BRCA2, RAD54L, and ATM. We did not observe a difference in age at diagnosis between DH carriers (median 56 years) and single BRCA1 carriers (median 51 years). There were no significant differences in other clinicopathological profiles (stage, pathology, tumor behavior, and survival) between the two groups. All the DH patients had a family history of multiple types of cancer. The presence of ovarian cancer family history was 66.7% (4/6) in DH group and 27.5% (19/69) in single BRCA1 PV group (p = 0.125). In comparison to single BRCA1 PV carriers, a higher percentage of family history of non-ovarian or breast cancer (100% vs. 46.4%, p = 0.025) was observed in DH carriers.
conclusionsOur study suggests that BRCA1 variant seems to drive the phenotypic expressions of ovarian cancer patients with DH. The management of these patients might be like BRCA1-mutated patients. Harboring DH may further increase the family member's chance of acquiring cancer of various types.
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