Abstract
Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer: An Oncology Research Information Exchange Network (ORIEN) analysis
Gynecologic oncology, Vol.190(Supplement 1), pp.S118-S119
11/2024
DOI: 10.1016/j.ygyno.2024.07.173
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 the 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 were collected for 788 ovarian cancer patients, including 71 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
Most participants were White (90.4 %). The mean age at diagnosis was 58.6 years, and the mean BMI was 27.5 kg/m2. Appalachian women with ovarian cancer were more likely to be non-Hispanic (100 % vs 94.5 %; P = 0.04), older at the time of diagnosis (63 years vs 58 years; P = 0.0006), have a higher BMI (29.1 vs 27 kg/m2; P = 0.048), and diagnosed at a later stage (III/IV, 82.5 % vs 66.2 %; P = 0.0115) than non-Appalachian residents. In univariate analysis, women in Appalachia had poorer survival than non-Appalachian residents (HR: 2.16; P < 0.001; 95 % CI: 1.44–3.25). In a multivariate analysis including Appalachian status, age at diagnosis, BMI, and stage, Appalachian residence trended towards increased risk for worse survival but was not significant (HR: 1.63; P = 0.054; 95 % CI: 0.37–1.01), while older age at diagnosis (HR: 1.02; P = 0.005; 95 % CI: 1.01–1.04) and advanced stage (stage III vs I: HR: 2.49; P = 0.008; 95 % CI: 1.27–4.89; stage IV vs I: HR: 3.13; P = 0.002; 95 % CI: 1.52–6.43) were significantly associated with poorer survival. After correcting for multiple comparisons, significantly mutated genes in the Appalachian residents were TP53 (70 %) and RPL38 (2 %), while TP53 (61 %), PIK3CA (14 %), and ARID1A (13 %) were the most frequently mutated genes among non-Appalachian residents. The frequency of BRCA1/BRCA2 mutation in Appalachia was 7.8 %, compared to 14.7 % in the non-Appalachia cohort (P = 0.18). Immune cell composition analysis demonstrated multiple significant differences, with non-Appalachian residents having increased proportions of naïve B cells, regulatory T cells, gamma-delta T cells, resting natural killer cells, and M2 macrophages. However, Appalachian residents had an increased proportion of activated dendritic cells.
Conclusions
Women with ovarian cancer residing in Appalachia are older at the time of diagnosis, have a higher BMI, and are diagnosed at later stages compared to non-Appalachian residents. While the current Appalachian population size did not reach statistical significance, the hazard ratio was likely due to the later stage and age at diagnosis. Along with our other findings, this study suggests other factors, like variable mutation frequencies and immune activation, may contribute to excess mortality in the region and should be further explored.
Details
- Title: Subtitle
- Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer: An Oncology Research Information Exchange Network (ORIEN) analysis
- Creators
- Allison Swiecki-Sikora - University of KentuckyJinge Liu - University of KentuckyMichelle ChurchmanJinpeng Liu - Rutgers Cancer Institute of New JerseyDava Piecoro - University of KentuckyTaylor Rives - Rutgers Cancer Institute of New JerseyJulia Nagle - University of KentuckyAliza Leiser - Rutgers Cancer Institute of New JerseyEugenia Girda - Rutgers Cancer Institute of New JerseySheri Holmen - University of UtahJennifer Doherty - University of UtahJing-Yi Chern - Moffitt Cancer CenterRobert Wenham - Moffitt Cancer CenterBodour Salhia - University of Southern CaliforniaMarilyn Huang - University of VirginiaStephen Edge - Roswell Park Comprehensive Cancer CenterLaura Holman - University of Oklahoma Health Sciences CenterAbdul Rafeh Naqash - University of Oklahoma Health Sciences CenterBradley Corr - University of Colorado Anschutz Medical CampusBryan Schneider - Indiana University IndianapolisChi Wang - University of KentuckyCharles Dietrich - University of KentuckyJill Kolesar - University of Kentucky
- Resource Type
- Abstract
- Publication Details
- Gynecologic oncology, Vol.190(Supplement 1), pp.S118-S119
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ygyno.2024.07.173
- ISSN
- 0090-8258
- Language
- English
- Date published
- 11/2024
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984736760202771
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