Abstract C166: Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer - An Oncology Research Information Network (ORIEN) analysis
Authors: Swiecki-Sikora Allison L. , Liu Jinge , Churchman Michelle , Liu Jinpeng , Piecoro Dava , Rives Taylor A. , Nagle Julia , Girda Eugenia , Leiser Aliza , Holmen Sheri , Doherty Jennifer , Chern Jing-Yi , Wenham Robert , Salhia Bodour , Huang Marilyn , Edge Stephen , Holman Laura L. , Naqash Abdul Rafeh , Corr Bradley , Schneider Bryan , Wang Chi , Dietrich Charles S. , Kolesar Jill M. 
Published: September 2024

Abstract
Objectives: Few studies have examined the mutational landscape in ovarian cancers, and none have focused on the Appalachian region which has a higher incidence of ovarian cancer, higher rates of poverty, and limited access to care compared to non-Appalachian region. Women with ovarian cancer enrolled in the Total Cancer Care prospective cohort study were evaluated to compare overall survival, mutational landscape, and immune cell composition between subjects in Appalachian and Non-Appalachian regions. Methods: Clinical and genomic data are available for 627 ovarian cancer patients with varying histology, including 66 from Appalachian Kentucky. MutSigCV was used to identify significantly mutated genes. CIBERSORTx was used to estimate the immune cell composition based on RNA sequencing data. Fisher’s exact test was used to compare clinical and genomic characteristics, Cox regression analysis was used to compare survival, and Wilcoxon rank-sum was used to compare immune cell composition. Results: Appalachian women with ovarian cancer were more likely to be older at time of diagnosis (64 years vs 58 years, p= 0.003), have a higher BMI (28.8 vs 26.9 kg/m2, p= 0.045), and be diagnosed at the highest pathologic grade (Grade III, 90.3% vs 84.8%, p=0.023) than non-Appalachian residents. A higher proportion of Appalachian residents were diagnosed at advanced stage III/IV (85.9% vs 75.4%, p= 0.128). In univariate survival analysis, those residing in Appalachian areas had poorer survival than the non-Appalachian residents (HR1.92, 95% CI 1.25-2.94, p=0.0022). Appalachian status remained significantly associated with worse survival after adjusting for age, BMI and stage at diagnosis (HR 1.72, 95% CI 1.04-2.86, p=0.036). There was no significant difference between cohorts on histology of ovarian carcinomas. Multiple genes were significantly different between the two populations. The Appalachian cohort had more frequent PRF1 (8.3% vs 1.9%, p=0.013), MECOM (6.7% vs 1.3%, p=0.018), and ITGAV mutations (6.7% vs 1.5%, p=0.026). RECQL4, EZR, SRGAP3, USP6 were also significantly more frequent in Appalachian residents. LRP1B was the only gene significantly associated with non-Appalachian status (9.4% vs 1.7%, p= 0.047). When analyzing immune cell composition by Appalachian status, Appalachian residency was significantly associated with higher levels of activated dendritic cells. Non-Appalachian residents had non-significantly higher levels of M2 macrophages. Conclusion: Women with ovarian cancer residing in Appalachia are older at time of diagnosis, have a higher BMI, and are diagnosed at higher pathologic grade compared to non- Appalachian residents. Even after controlling for age, stage and BMI, Appalachian residence remained significantly associated with worse survival. Multiple mutations associated with oncogenesis were significantly over-represented in the Appalachian cohort, which may contribute to excess mortality in the region.
Citation Format: Allison L. Swiecki-Sikora, Jinge Liu, Michelle Churchman, Jinpeng Liu, Dava Piecoro, Taylor A. Rives, Julia Nagle, Eugenia Girda, Aliza Leiser, Sheri Holmen, Jennifer Doherty, Jing-Yi Chern, Robert Wenham, Bodour Salhia, Marilyn Huang, Stephen Edge, Laura L. Holman, Abdul Rafeh Naqash, Bradley Corr, Bryan Schneider, Chi Wang, Charles S. Dietrich, Jill M. Kolesar. Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer - An Oncology Research Information Network (ORIEN) analysis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C166.