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Gynecol Oncol. 2019 May;153(2):335-342. doi: 10.1016/j.ygyno.2019.02.028. Epub 2019 Feb 28.

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.

Author information

1
Division of Gynecologic Oncology, University of California at Dabvis, Sacramento, CA, United States of America. Electronic address: rebrooks@ucdavis.edu.
2
School of Public Health, University of Toronto, Toronto, ON, Canada.
3
Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America; Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, Inova Medical Campus, Falls Church, VA, United States of America.
4
Biopathology Center, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America; Division of Gynecologic Oncology, The Ohio State University, Columbus, OH, United States of America.
5
Division of Gynecologic Oncology, The Ohio State University, Columbus, OH, United States of America.
6
Division of Radiation Oncology, Ridgeview Medical Center, Waconia, MN, United States of America.
7
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Denver, CO, United States of America.
8
Department of Obstetrics and Gynecology, Program in Women's Oncology, Women & Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States of America.
9
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Penn State College of Medicine, Milton S. Hershey Medical Center, United States of America.
10
Department of Obstetrics, Gynecology, and Reproductive Services, University of Pittsburgh Medical Center, Magee-Women's Hospital, Pittsburgh, PA, United States of America.
11
Department of OB/GYN, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
12
Department of Obstetrics and Gynecology, Case Western Reserve University, Cleveland, OH, United States of America.
13
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, United States of America.
14
Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, United States of America.
15
Department of Obstetrics and Gynecology, Springfield Clinic, Springfield, IL, United States of America.
16
Division of Gynecologic Oncology and Siteman Cancer Center, Washington University, St Louis, MO, United States of America.
17
Division of Hematology Oncology, The University of Alabama, Birmingham, AL, United States of America.

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.

KEYWORDS:

Endometrial cancer; Node positivity; Risk stratification; SNP association

PMID:
30827726
PMCID:
PMC6486855
DOI:
10.1016/j.ygyno.2019.02.028
[Indexed for MEDLINE]
Free PMC Article

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