RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

Donghui Li, Jennifer Moughan, Christopher Crane, John P. Hoffman, William F. Regine, Ross A. Abrams, Howard Safran, Chang Liu, Ping Chang, Gary M. Freedman, Kathryn A. Winter, Chandan Guha, James L. Abbruzzese

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23,. P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70,. P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63,. P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

Original languageEnglish (US)
JournalInternational Journal of Radiation Oncology Biology Physics
DOIs
StateAccepted/In press - Jul 7 2015

Fingerprint

Radiation Oncology
polymorphism
Pancreatic Neoplasms
radiation therapy
Radiotherapy
cancer
Survival
gemcitabine
Genotype
hazards
confidence
alternating current
Confidence Intervals
intervals
rank tests
paraffins
Tissue Distribution
Proportional Hazards Models
Paraffin
availability

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer : A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704. / Li, Donghui; Moughan, Jennifer; Crane, Christopher; Hoffman, John P.; Regine, William F.; Abrams, Ross A.; Safran, Howard; Liu, Chang; Chang, Ping; Freedman, Gary M.; Winter, Kathryn A.; Guha, Chandan; Abbruzzese, James L.

In: International Journal of Radiation Oncology Biology Physics, 07.07.2015.

Research output: Contribution to journalArticle

Li, Donghui ; Moughan, Jennifer ; Crane, Christopher ; Hoffman, John P. ; Regine, William F. ; Abrams, Ross A. ; Safran, Howard ; Liu, Chang ; Chang, Ping ; Freedman, Gary M. ; Winter, Kathryn A. ; Guha, Chandan ; Abbruzzese, James L. / RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer : A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704. In: International Journal of Radiation Oncology Biology Physics. 2015.
@article{ebb01976bce5491c9ebb04edf580f600,
title = "RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704",
abstract = "Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37{\%} had genotype AA, 43{\%} AC, and 20{\%} CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95{\%} confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95{\%} CI 1.07-2.23,. P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95{\%} CI 0.99-2.70,. P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95{\%} CI 0.81-2.63,. P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.",
author = "Donghui Li and Jennifer Moughan and Christopher Crane and Hoffman, {John P.} and Regine, {William F.} and Abrams, {Ross A.} and Howard Safran and Chang Liu and Ping Chang and Freedman, {Gary M.} and Winter, {Kathryn A.} and Chandan Guha and Abbruzzese, {James L.}",
year = "2015",
month = "7",
day = "7",
doi = "10.1016/j.ijrobp.2015.10.062",
language = "English (US)",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer

T2 - A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

AU - Li, Donghui

AU - Moughan, Jennifer

AU - Crane, Christopher

AU - Hoffman, John P.

AU - Regine, William F.

AU - Abrams, Ross A.

AU - Safran, Howard

AU - Liu, Chang

AU - Chang, Ping

AU - Freedman, Gary M.

AU - Winter, Kathryn A.

AU - Guha, Chandan

AU - Abbruzzese, James L.

PY - 2015/7/7

Y1 - 2015/7/7

N2 - Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23,. P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70,. P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63,. P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

AB - Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23,. P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70,. P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63,. P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

UR - http://www.scopus.com/inward/record.url?scp=84951098383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951098383&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2015.10.062

DO - 10.1016/j.ijrobp.2015.10.062

M3 - Article

C2 - 26725729

AN - SCOPUS:84951098383

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

ER -