Donghui Li1, Jennifer Moughan2, Christopher Crane3, John P Hoffman4, William F Regine5, Ross A Abrams6, Howard Safran7, Chang Liu3, Ping Chang3, Gary M Freedman8, Kathryn A Winter2, Chandan Guha9, James L Abbruzzese10. 1. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: dli@mdanderson.org. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. 3. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. 4. Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 5. Department of Radiation Oncology, University of Maryland, Baltimore, Maryland. 6. Rush University Medical Center, Chicago, Illinois. 7. Brown University Oncology Group, Providence, Rhode Island. 8. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. 9. Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York. 10. Duke University Medical Center, Durham, North Carolina.
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.
PURPOSE: To confirm whether a previously observed association between RECQ1A159C variant and clinical outcome of resectable pancreatic cancerpatients 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 RECQ1A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancerpatients 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: Kevin M Doherty; Sudha Sharma; Laura A Uzdilla; Teresa M Wilson; Sheng Cui; Alessandro Vindigni; Robert M Brosh Journal: J Biol Chem Date: 2005-05-09 Impact factor: 5.157
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Authors: Sudha Sharma; Deborah J Stumpo; Adayabalam S Balajee; Cheryl B Bock; Peter M Lansdorp; Robert M Brosh; Perry J Blackshear Journal: Mol Cell Biol Date: 2006-12-11 Impact factor: 4.272
Authors: T Kawabe; N Tsuyama; S Kitao; K Nishikawa; A Shimamoto; M Shiratori; T Matsumoto; K Anno; T Sato; Y Mitsui; M Seki; T Enomoto; M Goto; N A Ellis; T Ide; Y Furuichi; M Sugimoto Journal: Oncogene Date: 2000-09-28 Impact factor: 9.867