Abstract
Abstract Introduction: Ovarian cancer is a heterogeneous disease; each histotype has distinct molecular origins, risk factors and outcomes. While it is well established that ovarian cancer has a familial risk component, the familiality of ovarian cancer histotypes has not been well described. The Utah Population Database (UPDB) captures over 10 million individuals, including more than 5 million with a minimum of three generations of genealogy data. By linking records from the UPDB to the Utah Cancer Registry (UCR) and other statewide data sources, we sought to describe the familiality of ovarian cancer histotypes. Methods: Our study includes all ovarian cancer cases in the UPDB and leverages clinical data reported to UCR for the case histotypes. Cases were matched to controls on age, birth cohort and at least three generations of UPDB data versus not. We quantified familiality by comparing the odds of ovarian cancer occurrence among family members of cases to the odds of ovarian cancer among family members of matched controls. We calculated odds ratios for first-degree relatives, second-degree relatives, and first cousins. Results: As of September 2018, the UPDB included 3,989 ovarian cancer cases. We observed an increased risk of epithelial ovarian cancer among first-degree relatives (OR=1.62, 95%CI=1.36-1.93), second-degree relatives (OR=1.53, 95%CI=1.34-1.74), and first cousins (OR=1.38, 95%CI=1.26-1.53) of ovarian cancer cases. When we analyzed epithelial ovarian cancers by histotype, familiality was most evident for high-grade serous, mucinous, and unclassified cancers. For example, we observed a 1.62-fold increased odds (95%CI=1.14-2.29) of high-grade serous ovarian cancer among the first-degree relatives of high-grade serous cases, and a 5.59-fold increased odds (95%CI=2.09-14.92) of mucinous ovarian cancer among first-degree relatives of mucinous ovarian cancer cases. Familiality patterns were less clear among endometrioid and clear cell cases. Conclusions: The UPDB has the potential to contribute greatly to family-based studies of the genetics of ovarian cancer histotypes. Despite the possible variations in quality of histotype data across generations, preliminary results suggest some histotypes may be particularly familial and good candidates for gene mapping studies. Work is ongoing to refine the histotype assignments for cases by performing pathology review using the 2014 World Health Organization guidelines. Analyses are also in progress to stratify analyses by BRCA mutation status, and to consider the potential for shared familiality across ovarian cancer histotypes and with cancers at other sites. Citation Format: Mollie E. Barnard, Nicola J. Camp, Jennifer A. Doherty. Familiality of ovarian cancer histotypes in the Utah Population Database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4174.
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