Abstract IA31: Molecular epidemiology of ovarian cancer

Abstract Epithelial ovarian cancer (EOC) accounts for 5% of all cancer deaths and is the fifth leading cause of cancer death in women in the United States. While the incidence is slightly higher in European Americans (EA) than in African American (AA) women, five-year relative survival is much worse for AA women at 36.4% compared to 44.3% for EA women. AA women also have a poorer survival for breast cancer and for both ovarian and breast cancer access to appropriate treatment is a major contributor. Additionally poorer breast cancer survival among AA women has been attributed to aggressive subtypes being more common in AA women compared to EA women. Although the definition of ovarian cancer subtypes has lagged behind that of breast cancer, there have been major changes in the understanding of EOC over the past decade where EOC is not seen as a single disease but as a heterogeneous group of distinct diseases with different morphologic, protein and gene expression profiles. There is now strong evidence that the diverse histologic types comprising ovarian cancer arise not primarily from the ovarian surface epithelium but from various extra-ovarian tissues. Systematic molecular characterization of the most common and lethal morphologic disease subgroup, high grade serous ovarian cancer (HGOSC), provides evidence that subtypes of HGSOC exist and are definable based on gene expression patterns. Four subtypes appear to have robust definitions across different datasets and populations, which resemble the TCGA subtypes labeled as mesenchymal, proliferative, differentiated, and immunoreactive. Most of the molecular profiles of HGSOC in AA women have been based on white cases, with only 24 AA cases available in the TCGA dataset and 29 AA cases in the North Carolina Ovarian Cancer Study. In our recent study which included 164 EA and 29 AA women enrolled in the North Carolina Ovarian Cancer Study, we reported differences in the relative proportion of the four HGOSC gene expression subtypes by race. Preliminary results of HGSOC gene expression patterns in a larger sample of cases enrolled in the African American Cancer Epidemiology Study (AACES), an ongoing multi-center population-based study, support the existence of similar and novel subtypes as reported in EA women with ovarian cancer. Additionally, intrinsic mutational subtypes have been described using the TCGA data of which four have been found to predict survival. However, these mutational subtypes were not found to correspond to the gene expression subtypes. The majority of the ovarian cancer cases were EA and further work in this area which specifically addresses AAs with ovarian cancer is warranted. Although there are over 20 known genome-wide ovarian cancer risk associated SNPs, none have yet been evaluated in AAs and most were determined among EA women. Evaluation of association with these susceptibility variants is currently underway in AA ovarian cancer cases and controls within the NCI-funded GAME-ON consortium. Nearly all EOC research has been performed in EA women with limited focus on racially diverse populations. Comparisons across populations will aid in precisely defining genetic association, molecular subtypes and identify subtype-specific features for future functional characterization with implications for improving treatment and understanding the etiology of one of the most deadly cancers. Below are research objectives that will address important gaps in the molecular epidemiology of ovarian cancer in African American women: Determine molecular subtypes among African-American womenEvaluate genetic risk variants for ovarian cancer susceptibility and survival in African-American womenIncorporate assessment of ovarian cancer risk of African Americans in risk prediction modelsDevelop evidence-based interventions to reduce risk and increase survival Citation Format: Joellen M. Schildkraut. Molecular epidemiology of ovarian cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA31.