Age-Specific Ovarian Cancer Risk Among Individuals With Pathogenic Variants in <i>PALB2</i>.

Abstract

Pathogenic germline variants (PGVs) in <i>PALB2</i> are well-established risk factors for breast cancer, but their association with ovarian cancer (OC) remains less characterized. This study estimates age-specific OC risk among <i>PALB2</i> PGV carriers using a Bayesian segregation analysis approach. Family history, including OC diagnoses, was collected from probands with PGVs in <i>PALB2</i> from the Clinical Cancer Genomics Cancer Research Network (CCGCRN). CCGCRN is a consortium of 31 active community-based oncogenetic practices across 50 states in the United States and four countries in Latin America. A total of 140 probands with PGVs in <i>PALB2</i> were identified in CCGCRN, and family history was reported on 5,188 relatives (average family size is 38 individuals). Overall, 30 women had OC; of these, 5 cases were among probands and the remaining were among reported relatives. Age-specific penetrance of OC was estimated using the <i>penetrance</i> R package that employs a parametric Bayesian segregation analysis estimation approach, leveraging the family history. The cumulative lifetime risk for OC for female carriers of <i>PALB2</i> PGVs at age 80 years was estimated to be 5.38% (95% CI [2.94 to 8.26]). This is significantly greater than the general population risk of 1.10% from the SEER data. We estimated a significantly increased risk of OC among individuals with <i>PALB2</i> PGVs compared with the SEER general population. However, our estimated credible interval was wide, likely because of the small sample number of probands and small number of OC cases. Further studies should continue to explore the association between PGVs in <i>PALB2</i> and OC risk.