Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: A replication study in RTOG 9704.

Abstract

156 Background: To confirm whether a previously observed association between a DNA repair gene and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population. Methods: We evaluated the RecQ1 A159C variant (rs13035) in patients with resected pancreatic cancer who were enrolled on the RTOG 9704 trial of 5FU-based chemoradiation preceded and followed by 5-FU or gemcitabine. DNA was extracted from paraffin-embedded tissue sections and genotype was determined using the Taqman method. A multivariate Cox proportional hazards model was used to determine if there is a correlation between genotype and overall survival (OS). Models were built using the stepwise selection procedure. The following variables were included in the model: genotype, treatment arm, age, gender, race, nodal involvement, tumor diameter, and surgical margin status. Results: A total of 154 out of 451 eligible patients were evaluated for the RecQ1genotype. There was no significant difference in baseline characteristics and overall survival time between patients who were and were not evaluated for the RecQ1genotype. In the 154 evaluated patients, the genotype distribution followed the Hardy-Weinberg Equilibrium, i.e. 37% had genotype AA, 43% AC, and 20% CC. The RecQ1 variant AC/CC genotype carriers were more likely to be node positive compared to the AA carrier (p=0.03). The median survival times (95% C.I.) for AA, AC, and CC carriers were 1.72 (1.36, 2.17), 1.57 (1.18, 1.80), and 1.18 (0.86, 1.75) years, respectively. On multivariate analysis, patients with the AC/CC genotypes were more likely to die than patients with AA genotype (HR=1.54, 95% C.I. = [1.07, 2.23], p=0.022). This effect is more definitive for patients on the 5-FU arm (n=82) (HR=1.64, 95% C.I. = [0.99, 2.70], p=0.055) than for patients on the gemcitabine arm (n=72, HR=1.46, 95% C.I. = [0.81, 2.63], p=0.21). Conclusions: Results of this study suggest that the RecQ1 A159C genotype is a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant chemoradiation. No significant financial relationships to disclose.