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. 2017 Nov;147(2):396-401.
doi: 10.1016/j.ygyno.2017.08.024. Epub 2017 Sep 19.

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  1 , David Tritchler  2 , Kenneth M Kaufman  3 , Heather Lankes  4 , Michael C J Quinn  5 ; Ovarian Cancer Association Consortium; Linda Van Le  6 , Andrew Berchuck  7 , Floor J Backes  8 , Krishnansu S Tewari  9 , Roger B Lee  10 , Joshua P Kesterson  11 , Robert M Wenham  12 , Deborah K Armstrong  13 , Thomas C Krivak  14 , Michael A Bookman  15 , Michael J Birrer  16
Affiliations

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 et al. Gynecol Oncol. 2017 Nov.

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.

Keywords: Advanced stage serous ovarian; Genome-wide association; Primary peritoneal cancer.

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Conflict of interest statement

Conflict of interest statement

The authors report the following conflicts of interest: K. Moore reports advisory board participation for Astra Zeneca, Clovis, Immunogen, Tesaro, Genentech/Roche, Advaxis, VBL Therapeutics and Janssen. L. van Lee reports clinical trial grants from Astra Zeneca and Morphotek. K Tewari reports speakers bureau participation for Genentech/Roche, Merck, Astra Zeneca, Vermillion, and Clovis. He also reports steering committee participation with Mateon and consultancy with CARIS. R.Wenham reports speakers bureau participation for Genentech/Roche and Janssen as well as steering committee participation for Tesaro. M Bookman reports advisory board participation with Astra Zenca, Tesaro, Endocyte, Pfizer and Clovis. He reports steering committee participation for Genentech/Roche, Mateon and Abbvie and employment with McKesson Specialty Health and USOR. D. Tritchler, K. Kaufman, H. Lankes, M Quinn, A Berchuck, F Backes, R Lee, J Kesterson, D Armstrong, T Krivak and M Birrer have nothing to disclose.

Figures

Fig. 1
Fig. 1
Manhattan plot for overall survival. The horizontal red line displays the Bonferroni threshold which was not crossed by any polymorphism indicating lack of statistical significance.
Fig. 2
Fig. 2
Manhattan plot for progression free survival. The horizontal red line displays the Bonferroni threshold which was not crossed by any polymorphism indicating lack of statistical significance.
See this image and copyright information in PMC

References

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