e14590 Background: Pancreatic cancer (PaCa) is the 4th leading cause of cancer-related mortality in the U.S . We tried to determine whether ATM, RecQ1 gene polymorphisms correlate with gemcitabine (G) and TSER gene polymorphism with capecitabine (C) response and over all survival(OS). We also tested the hypothesis that PaCa pts homozygous for the S/S variant of the TSER will have a higher 6-month survival with C compared to historical controls. TS expression is regulated by a polymorphism in the TSER and has been shown that pts with S/S variant have high response rate and increased toxicity in colon cancer pts. ATM and recQ1 genes are involved with DNA damage response and repair and correlate with G response.Methods: DNA isolated from peripheral blood samples in 82 pts with Stage IV pancreatic cancer was tested for the TSER, ATM and RecQ1 gene polymorphisms. All patients were treated with G 1,000mg/m2 wkly for 3/4 wks. Pts homozygous for the S/S variant were treated with C, 2,000 mg/m2/day for 14 /21days. Pts were evaluated for response to therapy according to the RECIST.Results: 16 pts (19.5%) were positive for S/S variant of TSER, but only 4 (4.8%) were treated. The reasons for declining treatment were geographic, logistic or progression issues. Only 1 pt was evaluable, receiving at least 3 cycles of C . All pts needed dose reductions due to toxicities. Grade 3 hand foot syndrome, diarrhea and vomiting were dose limiting toxicities. No complete or partial responses were seen. The pt who received 3 cycles came off study due to progressive disease and the other 3 pts came of the study due to toxicities. TSER polymorphism was correlated to OS and only S/S variant was significant with a trend towards improved OS by log rank test and Kaplan Meier plot. ATM and RecQ1 gene polymorphisms subtypes did not correlate with G response and OS ( not statistically significant).Conclusions: Our study represents an initial effort to apply pharmacogenetics to PaCa therapy. 19.5% of pts had the S/S variant of the TSER polymorphism, but only 4.8% enrolled. C administration was associated with excess toxicity. The toxicities observed in this study appear to outweigh the benefit of using C in this pt population. There is no correlation between ATM and RecQ1 genotypes with OS. However the sample size is too small to draw conclusions. [Table: see text].