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

Kathleen N. Moore, David Tritchler, Kenneth M. Kaufman, Heather Lankes, Michael C.J. Quinn, Linda Van Le, Andrew Berchuck, Floor J. Backes, Krishnansu S. Tewari, Roger B. Lee, Joshua P. Kesterson, Robert M. Wenham, Deborah Kay Armstrong, Thomas C. Krivak, Michael A. Bookman, Michael J. Birrer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - 2017

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Neoplasms
Survival
Optical Devices
Translational Medical Research
Optical Imaging
Gene Frequency
Quality Control
Biomarkers
DNA

Keywords

  • Advanced stage serous ovarian
  • Genome-wide association
  • Primary peritoneal cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

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. / Moore, Kathleen N.; Tritchler, David; Kaufman, Kenneth M.; Lankes, Heather; Quinn, Michael C.J.; Van Le, Linda; Berchuck, Andrew; Backes, Floor J.; Tewari, Krishnansu S.; Lee, Roger B.; Kesterson, Joshua P.; Wenham, Robert M.; Armstrong, Deborah Kay; Krivak, Thomas C.; Bookman, Michael A.; Birrer, Michael J.

In: Gynecologic Oncology, 2017.

Research output: Contribution to journalArticle

Moore, KN, Tritchler, D, Kaufman, KM, Lankes, H, Quinn, MCJ, Van Le, L, Berchuck, A, Backes, FJ, Tewari, KS, Lee, RB, Kesterson, JP, Wenham, RM, Armstrong, DK, Krivak, TC, Bookman, MA & Birrer, MJ 2017, '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', Gynecologic Oncology. https://doi.org/10.1016/j.ygyno.2017.08.024
Moore, Kathleen N. ; Tritchler, David ; Kaufman, Kenneth M. ; Lankes, Heather ; Quinn, Michael C.J. ; Van Le, Linda ; Berchuck, Andrew ; Backes, Floor J. ; Tewari, Krishnansu S. ; Lee, Roger B. ; Kesterson, Joshua P. ; Wenham, Robert M. ; Armstrong, Deborah Kay ; Krivak, Thomas C. ; Bookman, Michael A. ; Birrer, Michael J. / 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. In: Gynecologic Oncology. 2017.
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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.",
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T1 - Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer

T2 - An NRG Oncology/Gynecologic Oncology Group study

AU - Moore, Kathleen N.

AU - Tritchler, David

AU - Kaufman, Kenneth M.

AU - Lankes, Heather

AU - Quinn, Michael C.J.

AU - Van Le, Linda

AU - Berchuck, Andrew

AU - Backes, Floor J.

AU - Tewari, Krishnansu S.

AU - Lee, Roger B.

AU - Kesterson, Joshua P.

AU - Wenham, Robert M.

AU - Armstrong, Deborah Kay

AU - Krivak, Thomas C.

AU - Bookman, Michael A.

AU - Birrer, Michael J.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Advanced stage serous ovarian

KW - Genome-wide association

KW - Primary peritoneal cancer

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