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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.

Publication ,  Journal Article
Brooks, RA; Tritchler, DS; Darcy, KM; Lankes, HA; Salani, R; Sperduto, P; Guntupalli, S; DiSilvestro, P; Kesterson, J; Olawaiye, AB; Moxley, K ...
Published in: Gynecol Oncol
May 2019

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.

Duke Scholars

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

May 2019

Volume

153

Issue

2

Start / End Page

335 / 342

Location

United States

Related Subject Headings

  • Risk Assessment
  • Progression-Free Survival
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • NM23 Nucleoside Diphosphate Kinases
  • Middle Aged
  • Lymphatic Metastasis
  • Humans
 

Citation

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Brooks, R. A., Tritchler, D. S., Darcy, K. M., Lankes, H. A., Salani, R., Sperduto, P., … Goodfellow, P. J. (2019). 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. Gynecol Oncol, 153(2), 335–342. https://doi.org/10.1016/j.ygyno.2019.02.028
Brooks, Rebecca A., David S. Tritchler, Kathleen M. Darcy, Heather A. Lankes, Ritu Salani, Paul Sperduto, Saketh Guntupalli, et al. “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.Gynecol Oncol 153, no. 2 (May 2019): 335–42. https://doi.org/10.1016/j.ygyno.2019.02.028.
Brooks RA, Tritchler DS, Darcy KM, Lankes HA, Salani R, Sperduto P, Guntupalli S, DiSilvestro P, Kesterson J, Olawaiye AB, Moxley K, Waggoner S, Santin A, Rader JS, Kizer NT, Thaker PH, Powell MA, Mutch DG, Birrer MJ, Goodfellow PJ. 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. Gynecol Oncol. 2019 May;153(2):335–342.
Journal cover image

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

May 2019

Volume

153

Issue

2

Start / End Page

335 / 342

Location

United States

Related Subject Headings

  • Risk Assessment
  • Progression-Free Survival
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • NM23 Nucleoside Diphosphate Kinases
  • Middle Aged
  • Lymphatic Metastasis
  • Humans