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

doi:10.1016/j.ygyno.2019.02.028

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 journal › Article › peer-review

5 Scopus citations

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 language	English (US)
Pages (from-to)	335-342
Number of pages	8
Journal	Gynecologic Oncology
Volume	153
Issue number	2
DOIs	https://doi.org/10.1016/j.ygyno.2019.02.028
State	Published - May 2019

All Science Journal Classification (ASJC) codes

Oncology
Obstetrics and Gynecology

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10.1016/j.ygyno.2019.02.028

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Brooks, R. A., Tritchler, D. S., Darcy, K. M., Lankes, H. A., Salani, R., Sperduto, P., Guntupalli, S., DiSilvestro, P., Kesterson, J., Olawaiye, A. B., Moxley, K., Waggoner, S., Santin, A., Rader, J. S., Kizer, N. T., Thaker, P. H., Powell, M. A., Mutch, D. G., Birrer, M. J., & 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. Gynecologic Oncology, 153(2), 335-342. https://doi.org/10.1016/j.ygyno.2019.02.028

@article{d0b60dedd11e48cfb9c96c9cb2ca6e5d,

title = "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",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = may,

doi = "10.1016/j.ygyno.2019.02.028",

language = "English (US)",

volume = "153",

pages = "335--342",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "2",

}

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 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', Gynecologic Oncology, vol. 153, no. 2, pp. 335-342. https://doi.org/10.1016/j.ygyno.2019.02.028

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. / Brooks, Rebecca A.; Tritchler, David S.; Darcy, Kathleen M. et al.
In: Gynecologic Oncology, Vol. 153, No. 2, 05.2019, p. 335-342.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - GOG 8020/210

T2 - Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study

AU - Brooks, Rebecca A.

AU - Tritchler, David S.

AU - Darcy, Kathleen M.

AU - Lankes, Heather A.

AU - Salani, Ritu

AU - Sperduto, Paul

AU - Guntupalli, Saketh

AU - DiSilvestro, Paul

AU - Kesterson, Joshua

AU - Olawaiye, Alexander B.

AU - Moxley, Katherine

AU - Waggoner, Steven

AU - Santin, Alessandro

AU - Rader, Janet S.

AU - Kizer, Nora T.

AU - Thaker, Premal H.

AU - Powell, Matthew A.

AU - Mutch, David G.

AU - Birrer, Michael J.

AU - Goodfellow, Paul J.

PY - 2019/5

Y1 - 2019/5

N2 - 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.

AB - 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.

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U2 - 10.1016/j.ygyno.2019.02.028

DO - 10.1016/j.ygyno.2019.02.028

M3 - Article

C2 - 30827726

AN - SCOPUS:85062102235

SN - 0090-8258

VL - 153

SP - 335

EP - 342

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 2

ER -

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

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