The Prognostic and Predictive Value of Dihydropyrimidine Dehydrogenase-Related Indicators in Clinical Outcomes of Chemotherapy in Colorectal Cancer Patients: a Systematic Review and Meta-Analysis.
Immunohistochemical localization of 5-FU metabolic enzymes (TS, MTHFR, DPYD, and TP) was evaluated in 143 untreated patients with colorectal cancer; their prognostic and predictive values were also evaluated.
We analysed more than 200 potentially functional, common, inherited variants in genes within the 5FU, capecitabine, oxaliplatin and DNA repair pathways, together with four rare dihydropyrimidine dehydrogenase (DPYD) variants, in 2183 aCRC patients treated with oxaliplatin-fluoropyrimidine chemotherapy with, or without, cetuximab (from MRC COIN and COIN-B trials).
Value of plasma SN-38 levels and DPD activity in irinotecan-based individualized chemotherapy for advanced colorectal cancer with heterozygous type UGT1A1<sup>*</sup>6 or UGT1A1<sup>*</sup>28.
Analyses of KRAS mutations in metastatic colorectal cancer, EGFR mutations in advanced non-small cell lung cancer, CYP2D6 polymorphism in breast cancer, DPD polymorphism in colorectal cancer and MTHFR polymorphism in osteosarcoma have been performed by real time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP).
In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).
The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer.
A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS.
No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.
This review summarizes the current knowledge about the splice isoforms of VEGFA, UGT1A, PXR, cyclin D1, BIRC5 (survivin), DPD, K-RAS, SOX9, SLC39A14 and other genes, which may be possible therapeutic targets for colorectal cancer.
Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer.
MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy.
In the present study, multiple CpG methylations of three genes (CDKN2A, DPYD and MLH1) were detected in DNA samples from patients with colorectal cancer using Pyrosequencing(R) technology.
Intratumoral DPD mRNA expression level was significantly higher in pancreatic cancer than that in colorectal cancer (P = 0.0003; median level, 1.38 vs. 0.44) and gastric cancer (P = 0.0061; 1.38 vs. 0.82).
The DPD mRNA level and OPRT/DPD ratio evaluated from paraffin embedded specimens are candidates for further evaluation as predictors of response against 5-fluorouracil-based chemotherapy in colorectal cancer.
Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer.
The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated.
Therefore, we examined the type and frequency of polymorphisms in the TYMS and DPYD genes in 100 healthy Korean individuals and compared these findings with 21 patients with colorectal cancer who had a grade 3 or greater toxic response to 5-FU treatment.