[1590] Impact of Glutathione S- Transferase P 1 GSTP1) Polymorphism on Survival of Patients with Unresectable Pancreas Cancer Receiving Multimodal Therapies

YF Jin, T Ioka, M Song, M Tomoeda, S Nagata, M Kitamura, M Yuki, H Yoshizawa, C Kubo, Y Nishizawa, Y Tomita. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Osaka Prefecture, Japan

Background: Pancreatic ductal adenocarcinoma (PDAC) is still one of the most fatal cancers, although its prognosis has improved recently with the introduction of multimodal therapy. Most patients with IVa or IVb stage pancreatic cancer receive chemo- or chemoradiotherapy, however correlation between response to treatment and host genotyping of genes involved in detoxification of cytotoxic drugs has not been well-examined.
Design: Our retrospective analysis included 247 patients, who were diagnosed as having primary PDAC (WHO classification: stage IVa and IVb). Treatment regimens during the entire disease process were collapsed into 3 groups: TS1-based therapy, GEM-based therapy, and TS1/GEM-based therapy.Ile105Val polymorphism of the GSTP1 gene was analyzed using the PCR-RFLP technique from peripheral blood samples.
Results: Patients receiving TS1-based therapy showed a more favorable prognosis compared to those with other therapy in patients with GSTP1 Ile/Val or Val/Val, but not in patients with GSTP1 Ile/Ile. Patients receiving TS1/GEM-based therapy showed a more favorable prognosis compared to those with other therapy in patients with GSTP1 Ile/Ile, but not in patients with Ile/Val or Val/Val.

TABLE 1 Treatment Modality and Overall Survival by GSTP1105 Polymorphisms patients With Pancreatic cancer
Treatment ModalityIle/IleIle/Val ande Val/Val
No.of patient/deathsMS, MonthsPNo.of patient/deathsMS, MonthsP
TS1-base1:received51/3912.620.4915/1015.540.03
2:No received13011310.8941/369.38
GEM-base1:received150/12410.980.338/2910.360.66
2:No received41/2812.9518/1710.85
TS1/GEM-base1:received65/4816.43<.000125/2312.820.67
2:No received126/1049.2131/239.44
MS: medial survival


Conclusions: Favorable prognosis of patients with GSTP1105Val variant receiving TS1-based therapy was demonstrated. For those with 105Ile/Ile, TS1/GEM-based therapy proved as the most efficient treatment modality. Further in-depth study is necessary to clarify the molecular regulatory mechanism of chemotherapeutic reagents against cancers in each genetic variation.
Category: Liver & Pancreas

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 214, Tuesday Afternoon

 

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