Naslov
TYMS and DPYD polymorphisms and toxicity of 5-fluorouracil and capecitabine chemotherapy in colon cancer patients

Autori
Jokić, Mladen ; Gamulin, Marija ; Poparić, Ivana ; Grgić, Mislav ; Kapitanović, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the EORTC-NCI-ASCO Annual Meeting on 'Molecular Markers in Cancer' ; u: European Journal of Cancer. Supplement 7 (2009) (S4) ; PP104 / Smyth, John - Oxford : Elsevier, 2009, 20-20

Skup
EORTC-NCI-ASCO Annual Meeting on 'Molecular Markers in Cancer'

Mjesto i datum
Bruxelles, Belgija, 15.10.2009. - 17.10.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
TYMS; DPYD; toxicity; colon cancer

Sažetak
Thymidylate synthase (TS) is key enzyme in the synthesis of thymidylate and is a target for 5-FU which is mainly catabolised by dihydropyrimidine dehydrogenase (DPD). VNTR and C>T SNP in the enhancer region of TYMS gene (TSER) as well as DPYD gene mutation (DPYD*2A) may influence toxicity of 5FU/Capecitabine-based chemotherapy. Aim of this study was to evaluate the correlation between TSER VNTR and the susceptibility to sporadic colon cancer and to correlate the genotype frequencies of TSER VNTR and DPYD*2A between Croatian and other european populations. We also aimed to correlate TSER polymorphisms and DPYD*2A and toxicity of 5FU/Capecitabine-based chemotherapy in colon cancer patients. Genotyping was performed on 100 healthy unrelated Croatians and 100 colon cancer patients using PCR-RFLP method. Genotype frequencies of TSER VNTR did not differ statistically between controls and colon cancer patients. 49 patients were assesed for toxicity and two patients with worst toxicities were heterozygous for DPYD*2A. Among the remaining 47 patients, 33 were assigned into a 'low expression TSER genotype' group (13 (39, 4%) with 2R/2R, 12 (36, 4%) with 2R/3RC and 8 (24, 2%) with 3RC/3RC TSER genotype) and 14 into a 'high expression TSER genotype' group (7 (50, 0%) with 2R/3RG, 1 (7, 14%) with 3RG/3RG and 6 (42, 86%) with 3RG/3RC TSER genotype). 25 patients (75, 76%) from a 'low expression TSER genotype' group experienced a total of 65 toxicities. 6 patients (42, 86%) from a 'high expression' group experienced total of 10 toxicities. No correlation was found between TSER VNTR and the susceptibility to sporadic colon cancer. Genotype and allele frequencies were similar to other european populations. We assume that the worst toxicities experienced by two patients with DPYD*2A mutation were a consequence of that mutation but due to a small patient number, the impact of this mutation on risk of toxicity could not be proven to be statistically significant. The remaining forty-seven colon cancer patients were divided into two groups based on TSER genotype. 'Low expression TSER genotype' group of patients suffered from more and worse toxicities (grade III and IV) of 5FU/Capecitabine-based chemotherapy compared to a 'high expression TSER genotype' group (p=0.020606, p<0, 0001, respectively). These results might have a prognostic role in the prediction of toxicity of 5FU/Capecitabine-based chemotherapy in colon cancer patients in Croatia.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA