Kathleen N Moore1, David Tritchler2, Kenneth M Kaufman3, Heather Lankes4, Michael C J Quinn5, Linda Van Le6, Andrew Berchuck7, Floor J Backes8, Krishnansu S Tewari9, Roger B Lee10, Joshua P Kesterson11, Robert M Wenham12, Deborah K Armstrong13, Thomas C Krivak14, Michael A Bookman15, Michael J Birrer16. 1. Stephenson Oklahoma Cancer Center at the University of Oklahoma, Oklahoma City, OK, USA. Electronic address: Kathleen-moore@ouhsc.edu. 2. The Gynecologic Oncology Group Biostatistics Office, Buffalo, NY, USA. 3. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. Electronic address: Kenneth.kaufman@cchmc.org. 4. Statistics and Data Management Center, NRG Oncology, Buffalo, NY, USA. Electronic address: hlankes@gogstats.org. 5. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Electronic address: Michael.quinn@qimrberghofer.edu.au. 6. UNC, Chapel Hill, Department of OB/GYN, Chapel Hill, NC 27599, USA. Electronic address: lvl@med.unc.edu. 7. Duke University Medical Center, Room 25172, Durham, NC 27710, USA. Electronic address: berch001@mc.duke.edu. 8. Ohio State University, Wexner Medical Center, Hilliard, OH 43026, USA. Electronic address: Floor.Backes@osumc.edu. 9. University of California Medical Center, Irvine, CA 92868, USA. Electronic address: ktewari@uci.edu. 10. Tacoma General Hospital, Tacoma, WA, USA. 11. Penn State Medical Center, Hershey, PA, USA. Electronic address: jkesterson@pennstatehealth.psu.edu. 12. Moffitt Cancer Center, Tampa, FL, USA. Electronic address: Robert.wenham@moffitt.org. 13. Sidney Kimmel Cancer Center, Division of Medical Oncology, John Hopkins, Baltimore, MD, USA. Electronic address: armstde@jhmi.edu. 14. Western Pennsylvania Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Pittsburgh, PA, USA. Electronic address: Thomas.krivak@plzdocs.com. 15. Gynecologic Oncology Research, US Oncology Research Arizona Oncology, Tucson, AZ 85711, USA. Electronic address: michael.bookman@usoncology.com. 16. Gynecological Oncology, Massachusetts General Hospital, Department of Medicine, Boston, MA, USA. Electronic address: MBIRRER@mgh.harvard.edu.
Abstract
OBJECTIVE: This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. METHODS: Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency>0.05 and genotyping rate>0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p-values with genomic control adjustment. RESULTS: The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e-08. No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p-2.144e-08) (rs6256 p-9.774e-07) for PFS and 2 different SNPs were identified (rs295315 p-7.536e-07; rs17693104 p-7.734e-07) which were close to significance for OS. CONCLUSIONS: Using the pre-specified level of significance of 1×10-08, we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers.
OBJECTIVE: This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. METHODS: Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency>0.05 and genotyping rate>0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p-values with genomic control adjustment. RESULTS: The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e-08. No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p-2.144e-08) (rs6256 p-9.774e-07) for PFS and 2 different SNPs were identified (rs295315 p-7.536e-07; rs17693104 p-7.734e-07) which were close to significance for OS. CONCLUSIONS: Using the pre-specified level of significance of 1×10-08, we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers.
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Authors: Michael C J Quinn; Karen McCue; Stuart MacGregor; Georgia Chenevix-Trench; Wei Shi; Sharon E Johnatty; Jonathan Beesley; Andrew Civitarese; Tracy A O'Mara; Dylan M Glubb; Jonathan P Tyrer; Sebastian M Armasu; Jue-Sheng Ong; Puya Gharahkhani; Yi Lu; Bo Gao; Ann-Marie Patch; Peter A Fasching; Matthias W Beckmann; Diether Lambrechts; Ignace Vergote; Digna R Velez Edwards; Alicia Beeghly-Fadiel; Javier Benitez; Maria J Garcia; Marc T Goodman; Thilo Dörk; Matthias Dürst; Francesmary Modugno; Kirsten Moysich; Andreas du Bois; Jacobus Pfisterer; Klaus Bauman; Beth Y Karlan; Jenny Lester; Julie M Cunningham; Melissa C Larson; Bryan M McCauley; Susanne K Kjaer; Allan Jensen; Claus K Hogdall; Estrid Hogdall; Joellen M Schildkraut; Marjorie J Riggan; Andrew Berchuck; Daniel W Cramer; Kathryn L Terry; Line Bjorge; Penelope M Webb; Michael Friedlander; Tanja Pejovic; Melissa Moffitt; Rosalind Glasspool; Taymaa May; Gabrielle E V Ene; David G Huntsman; Michelle Woo; Michael E Carney; Samantha Hinsley; Florian Heitz; Sian Fereday; Catherine J Kennedy; Stacey L Edwards; Stacey J Winham; Anna deFazio; Paul D P Pharoah; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-06-23 Impact factor: 4.090