TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients

Fariña-Sarasqueta, Arantza; Gosens, Marleen J.E.M.; Moerland, Elna; Lijnschoten, Ineke van; Lemmens, Valery; Slooter, Gerrit D.; Rutten, H.J.T.; Brule, Adriaan J. C. van den

doi:10.1007/s13402-011-0030-z

Cited by 9 publications

(7 citation statements)

References 40 publications

(55 reference statements)

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“…Several studies have noted that a C SNP was associated with longer PFS in colorectal cancer patients treated with 5-FU (21,22). However, several other studies did not find any significant difference between TS SNPs and the clinical outcome of patients treated with 5-FU (23–25). …”

Section: Discussionmentioning

confidence: 81%

Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy

Hua

Fang

et al. 2013

Oncology Letters

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The aim of this study was to evaluate the association between thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (SLC19A1) gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in the TS, MTHFR and SLC19A1 genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with the SLC19A1 CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes of MTHFR assessed. The RR was higher in patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5′-UTR of the TS gene and exon 6 (2522) C/T of the SLC19A1 gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.

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Section: Discussionmentioning

confidence: 81%

Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy

Hua

Fang

et al. 2013

Oncology Letters

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“…We found that patients born from 1943 onwards had more frequently the polymorphism 3RG/3RG and high-grade malignancy tumors (RR 1.730, 95%CI: 1.088-2.747; P = 0.030). Two previous studies have also linked age to TYMS polymorphisms and protein expression in CRC[53,54]. As more data gather, the differences in the frequency of polymorphisms among generations are of great interest.…”

Section: Discussionmentioning

confidence: 99%

TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer

Ntavatzikos¹,

Spathis²,

Patapis³

et al. 2019

WJGO

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BACKGROUND Patients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase ( TYMS ) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration. AIM To investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with chemotherapy. METHODS A retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (m KRAS ) and BRAF (m BRAF ). Patients were classified into three groups (high, medium and low risk) according to 5’UTR TYMS polymorphisms Similarly, based on 3’UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5-year survival outcomes. RESULTS One hundred and thirty patients with early stage CRC (stage I-II: 55 patients; stage III 75 patients; colon: 70 patients; rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5’UTR polymorphisms of intermediate TYMS polymorphisms (2RG/3RG, 2RG/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3’UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence ( P = 0.001) and death ( P = 0.005). m BRAF (3.8% of patients) was associated with increased risk of death (HR 4.500, P = 0.022) whereas m KRAS (39% of patients) not. CONCLUSION Prospective validating studies are required to confirm whether 2RG/3RG, 2RG/LOH, 3RC/LOH, absence of ins/LOH and wild type BRAF may indicate patients at lower risk of relapse following adjuvant chemotherapy.

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“…For example, most ERCC1 SNP studies are performed on blood samples, and in the few that were done on tumor tissue, contradictory results were seen . In the case of thymidlylate synthase, even though small studies support its predictivity for 5‐FU response , the results are not able to be replicated in larger studies . Therefore, IHC remains the most practical and accurate methodology to measure the predictive biomarkers to predict therapy response in a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling in gastric cancer: Examining potential targets for chemotherapy

Miura

Johnston

Thomas

et al. 2014

Journal of Surgical Oncology

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TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients

Cited by 9 publications

References 40 publications

Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy

Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy

TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer

Molecular profiling in gastric cancer: Examining potential targets for chemotherapy

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