1. Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study
- Author
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Michael C.J. Quinn, Deborah K. Armstrong, Krishnansu S. Tewari, Michael J. Birrer, Floor J. Backes, Linda Van Le, Thomas C. Krivak, Roger B. Lee, D. Tritchler, Kenneth M. Kaufman, Robert M. Wenham, Joshua Kesterson, Heather A. Lankes, Michael A. Bookman, Andrew Berchuck, and Kathleen N. Moore
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Genome-wide association study ,Gynecologic oncology ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Statistical significance ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,SNP ,Genotyping ,Allele frequency ,Peritoneal Neoplasms ,Aged ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Aged, 80 and over ,Ovarian Neoplasms ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,Prognosis ,Cystadenocarcinoma, Serous ,Serous fluid ,Female ,business ,Genome-Wide Association Study - 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.
- Published
- 2017