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Background <p>Double 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.</p> Methods <p>This 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 <i>BRCA1</i>. In 75 <i>BRCA1</i> 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.</p> Results <p>Six patients harboring germline <i>BRCA1</i> variant and a concurrent germline variant in cancer-predisposed genes were identified. Coupling with <i>BRCA1</i> PV, the additional variant involved <i>MUTYH</i>/<i>RECQL4</i>, <i>RAD51C</i>, <i>RECQL4</i>, <i>BRCA2</i>, <i>RAD54L</i>, and <i>ATM</i>. We did not observe a difference in age at diagnosis between DH carriers (median 56 years) and single <i>BRCA1</i> 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 <i>BRCA1</i> PV group (<i>p</i> = 0.125). In comparison to single <i>BRCA1</i> PV carriers, a higher percentage of family history of non-ovarian or breast cancer (100% vs. 46.4%, <i>p</i> = 0.025) was observed in DH carriers.</p> Conclusions <p>Our study suggests that <i>BRCA1</i> variant seems to drive the phenotypic expressions of ovarian cancer patients with DH. The management of these patients might be like <i>BRCA1</i>-mutated patients. Harboring DH may further increase the family member’s chance of acquiring cancer of various types.</p>

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Clinicopathological features of Chinese ovarian cancer patients with double heterozygosity for cancer-predisposed genes

  • 期刊论文

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  • 发表日期：

    2025年8月28日

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  • Yikun Jin,
  • Wenyan Wang,
  • Manqi Wu,
  • Yiming Fan,
  • Tongxia Wang,
  • Cuiyu Huang,
  • Tong Gao,
  • Yan Liu,
  • Yuan Li,
  • Qiyu Liu,
  • Hongyan Guo

摘要

Background

Double 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.

Methods

This 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.

Results

Six 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.

Conclusions

Our 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.