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

on behalf of the Ovarian Cancer Association Consortium

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)
Pages (from-to)396-401
Number of pages6
JournalGynecologic Oncology
Volume147
Issue number2
DOIs
StatePublished - Nov 1 2017

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

@article{298ab2de475c47f19b98c35b38d6ddc7,
title = "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",
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.",
author = "{on behalf of the Ovarian Cancer Association Consortium} and Moore, {Kathleen N.} and David Tritchler and Kaufman, {Kenneth M.} and Heather Lankes and Quinn, {Michael C.J.} and {Van Le}, Linda and Andrew Berchuck and Backes, {Floor J.} and Tewari, {Krishnansu S.} and Lee, {Roger B.} and Joshua Kesterson and Wenham, {Robert M.} and Armstrong, {Deborah K.} and Krivak, {Thomas C.} and Bookman, {Michael A.} and Birrer, {Michael J.}",
year = "2017",
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language = "English (US)",
volume = "147",
pages = "396--401",
journal = "Gynecologic Oncology",
issn = "0090-8258",
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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. / on behalf of the Ovarian Cancer Association Consortium.

In: Gynecologic Oncology, Vol. 147, No. 2, 01.11.2017, p. 396-401.

Research output: Contribution to journalArticle

TY - JOUR

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 - on behalf of the Ovarian Cancer Association Consortium

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

AU - Wenham, Robert M.

AU - Armstrong, Deborah K.

AU - Krivak, Thomas C.

AU - Bookman, Michael A.

AU - Birrer, Michael J.

PY - 2017/11/1

Y1 - 2017/11/1

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.

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