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: OBJECTIVE
  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
  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.
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: dli@mdanderson.org.
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Crane
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Hoffman
authors.affiliation: Department of Radiation Oncology, University of Maryland, Baltimore, Maryland.
authors.forename: William F
authors.initials: WF
authors.lastname: Regine
authors.affiliation: Rush University Medical Center, Chicago, Illinois.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Abrams
authors.affiliation: Brown University Oncology Group, Providence, Rhode Island.
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Freedman
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.affiliation: Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York.
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D059248:Chemoradiotherapy / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D011110:Polymorphism, Genetic; D053484:RecQ Helicases / Q000235:genetics*; D015203:Reproducibility of Results; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C506725:RECQL protein, human; D053484:RecQ Helicases; D005472:Fluorouracil; D000093542:Gemcitabine