Risk of ovarian cancer in women with a pathogenic or likely pathogenic variant in NBN: a systematic review and meta-analysis

OBJECTIVE: NBN is a putative ovarian cancer susceptibility gene. The association between a pathogenic variant in NBN and ovarian cancer is not well established. We aimed to estimate the ovarian cancer risk in unselected women with an NBN pathogenic variant. DATA SOURCES: PubMed and Embase searched from inception to January 2026. ELIGIBILITY CRITERIA: Population: Women diagnosed with ovarian cancer undergoing germline sequencing of NBN (intervention). STUDY APPRAISAL AND SYNTHESIS METHODS: We followed a prospective protocol as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42024567791). The number of NBN pathogenic variants in ovarian cancer cases in included studies was pooled and an estimated odds calculated. This was compared to the odds of an NBN loss-of-function variant in Genome Aggregation Database v4.1 controls of matched ethnicities to obtain the odds ratio of ovarian cancer with an NBN pathogenic variant. We performed prespecified subgroup analyses for high-grade serous carcinoma and non-high-grade serous carcinoma, and those with a family history of ovarian cancer. RESULTS: Searches yielded 9025 studies; 57 studies (n=40,537) were included in our initial analysis: 36 in majority White cohorts (n=33,822) and 21 in non-White cohorts (n=6715). In the White cohorts, the odds ratio of ovarian cancer with an NBN pathogenic variant was 1.68 (95% confidence interval, 1.37-2.07; P