Pharmacogenetic database of colon cancer patients in Croatia – correlation with clinical data (CROSBI ID 545078)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Gamulin, Marija ; Jokić, Mladen ; Grgić, Mislav ; Kapitanović, Sanja
engleski
Pharmacogenetic database of colon cancer patients in Croatia – correlation with clinical data
Pharmacogenetics deals with inherited differences in the response to drugs. A major limitation that moderates the use of pharmacogenetic testing is the lack of prospective clinical trials demonstrating that such testing can improve the benefit/risk ratio of drug therapy. Significant heterogenity in the efficacy and toxicity of chemotherapy agents is consistently observed. The aim of our research is a prospective pharmacogenetic study to examine the frequency of SNPs in genes regulating chemotherapeutic metabolism and the correlation between known polymorphisms and colon cancer therapy in Croatian population. Pharmacogenetic markers that were analyzed in our study were: IVS14+1G>A (DPYD*2A), UGT1A1 and XRCC1 R399Q. This study was performed using PCR-RFLP method and real-time PCR Taqman® ; ; ; SNP genotyping assays. Strongly correlation between farmacogenetic genotypes and clinical data were found. DPD is the initial and rate-limiting enzyme in the catabolism of 5-FU and IVS14+1G>A mutation (DPYD*2A genotype) is associated with DPD deficiency and severe toxicity after the administration of 5-FU. DPYD*2A allele was noted in 2/46 patients (4.34%) who developed mucositis Grade 2, neutropenia Grade 2 and diarrhea Grade 2 during the 5-FU therapy. UGT1A1 is involved in glucuronidation of a prodrug of irinotecan and UGT1A1*28 variant is associated with the risk of severe diarrhea and/or neutropenia in patients receiving the drug. Of 46 patients, 23 (50%) were treated with irinotecan, 4 (17.39%) patients with UGT1A1*28/ UGT1A1*28 genotype had diarrhea Grade 2 and neutropenia Grade 2/3 and a bad therapy response. Seven patients (30.43%) with UGT1A1/ UGT1A1 genotype had a good and long response to therapy with irinotecan. XRCC1 polymorphism R399Q is known to influence outcome after platinum-based treatment and Gln/Gln genotype is associated with non responding to therapy. Of 20 patients who received oxaliplatine/5-FU, 5 (25%) with Lys/Lys genotype responded well to chemotherapy and 2 with Gln/Gln genotype not responded to therapy. We hope that the results of this project will be used in the future for improvement of colon cancer therapy in Croatia.
pharmacogenetics; colon cancer
doi:10.1093/annonc/mdn507
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Podaci o prilogu
viii67-viii67.
2008.
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objavljeno
Podaci o matičnoj publikaciji
Annals of oncology
33rd ESMO Congress Scientific Committee
Stockholm: Oxford Journals
0923-7534
Podaci o skupu
ESMO Congress (33 ; 2008)
poster
12.09.2008-16.09.2008
Stockholm, Švedska
Povezanost rada
Temeljne medicinske znanosti, Kliničke medicinske znanosti