An integrated analysis of the association between Ts gene polymorphisms and clinical outcome in gastric and colorectal cancer patients treated with 5-FU-based regimens

Abstract

Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.

Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy

“…Even though data on the TS genotypes in patients with SBA are lacking, previous studies in patients with CRC have suggested the ethnic difference in the distribution of TS genotypes (35). In the present study, 3R/3R was the most prevalent allele with a frequency of 57%, whereas 2R/2R and 2R/3R occurred at frequencies of 10 and 33%, respectively.…”

Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

“…In the past years, several studies have been conducted to investigate the predictive value of TS gene polymorphisms (28-bp tandem repeat polymorphism in the 5′-UTR, a guanine instead of a cytosine (G/C) in 3R and 3′-UTR 6-bp deletion polymorphisms), and TS, DPD and TP expressions (most of them analyzed mRNA, rare detect protein) in cancer tissues, however, no proof-of-principle results can be drawn at this point222324252627282930313233. Our study demonstrated that none of the studied mSNPs can predict ORR or survival of GIC patients receiving first-line FU treatment independently and in addition we found that in TP : rs11479 T allele carriers (who may have higher TP level in tumor tissues), PC negatively correlated to OS of metastasis GIC patients, revealing the complexity among cancer progression, drug metabolism, tumor response to chemotherapy and the survival benefits.…”

A Functional Germline Variant in GLI1 Implicates Hedgehog Signaling in Clinical Outcome of Stage II and III Colon Carcinoma Patients

“…These common DNA-sequence variations may alter the gene function and/or activity, including transcription, translation, or splicing, thereby causing interindividual differences in relation to tumor recurrence capacity and chemoresistance (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Furthermore, common gene variants may also predict chemoresistance and toxicity to 5-fluorouracil (5-FU) and/or oxaliplatin as recently shown for the thymidylate synthetase, 5 methyltetrahydrofolate-homocysteine methyltransferase reductase, multidrug resistance protein 2, dihydropyrimidine dehydrogenase, and the X-ray repair cross-complementing protein 1 genes (30)(31)(32)(33)(34)(35).…”