GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study

Rebecca A. Brooks, David S. Tritchler, Kathleen M. Darcy, Heather A. Lankes, Ritu Salani, Paul Sperduto, Saketh Guntupalli, Paul DiSilvestro, Joshua Kesterson, Alexander B. Olawaiye, Katherine Moxley, Steven Waggoner, Alessandro Santin, Janet S. Rader, Nora T. Kizer, Premal H. Thaker, Matthew A. Powell, David G. Mutch, Michael J. Birrer, Paul J. Goodfellow

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients. Methods: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated. Results: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables. Conclusion: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalGynecologic Oncology
Volume153
Issue number2
DOIs
StatePublished - May 2019

Keywords

  • Endometrial cancer
  • Node positivity
  • Risk stratification
  • SNP association

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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