Partner and localizer of BRCA2 (PALB2) pathogenic variants and ovarian cancer: A systematic review and meta-analysis

Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), the role of partner and local...

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Published in:Gynecologic oncology 2023-10, Vol.177, p.72-85
Main Authors: Narayan, Priyanka, Ahsan, Muhammad Danyal, Webster, Emily M., Perez, Luiza, Levi, Sarah R., Harvey, Benedict, Wolfe, Isabel, Beaumont, Shanice, Brewer, Jesse T., Siegel, Drew, Thomas, Charlene, Christos, Paul, Hickner, Andy, Chapman-Davis, Eloise, Cantillo, Evelyn, Holcomb, Kevin, Sharaf, Ravi N., Frey, Melissa K.
Format: Article
Language:English
Subjects:
Genetics
Hereditary breast and ovarian cancer
Ovarian cancer
PALB2
Risk-reduction
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Summary:Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), the role of partner and localizer of BRCA2 (PALB2) remains uncertain. We sought to utilize meta-analysis to evaluate the association between PALB2 germline pathogenic variants and ovarian cancer. We conducted a systematic review and meta-analysis. We searched key electronic databases to identify studies evaluating multigene panel testing in people with ovarian cancer. Eligible trials were subjected to meta-analysis. Fifty-seven studies met inclusion criteria, including 52,505 people with ovarian cancer and information available on germline PALB2 pathogenic variant status. Among people with ovarian cancer and available PALB2 sequencing data, 0.5% [95% CI 0.4–0.7] harbored a germline pathogenic variant in the PALB2 gene. The pooled odds ratio (OR) for carrying a PALB2 pathogenic variant among the ovarian cancer population of 20,474 individuals who underwent germline testing was 2.48 [95% CI 1.57–3.90] relative to 123,883 controls. Our meta-analysis demonstrates that the pooled OR for harboring a PALB2 germline pathogenic variant among people with ovarian cancer compared to the general population is 2.48 (95% CI 1.57–3.90). Prospective studies evaluating the role of germline PALB2 pathogenic variants in the development of ovarian cancer are warranted. •There is emerging evidence that germline PALB2 pathogenic variants are associated with ovarian cancer.•Meta-analysis suggests that 0.5% [95% CI 0.4–0.7] of people with ovarian cancer may harbor a germline pathogenic variant in the PALB2 gene.•People with ovarian cancer are more than twice as likely to carry germline PALB2 pathogenic variants compared to controls.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2023.07.017