Genotype and allele frequencies of <i>TYMS</i>
 rs2790 A &gt; G polymorphism in a Chinese paediatric population with acute lymphoblastic leukaemia

Wang, Shu-Mei; Wei-xin, Zeng; Wu, Wanshui; Sun, Lulu; Yan, Dan

doi:10.1111/jcpt.12678

Cited by 4 publications

(4 citation statements)

References 20 publications

(46 reference statements)

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“…Critically, an understanding of how elevated levels of TS promote carcinogenic events could also help to explain why TS 3 -UTR polymorphisms may affect CRC occurrence and prognosis. According to a recent report, compared with the rs2790 AA genotype at the 3 -UTR of TS, the rs2790 GG genotype was associated with a significantly higher risk of acute lymphoblastic leukaemia (ALL) [37]. The present study confirmed that the presence of the TS 3 UTR polymorphism (rs151264360) increased the risk of persistence of cervical cancer [38].…”

Section: Discussionsupporting

confidence: 83%

3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis

Jeon

Cho

Kim

et al. 2021

JPM

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Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3′-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.

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Section: Discussionsupporting

confidence: 83%

3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis

Jeon

Cho

Kim

et al. 2021

JPM

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“…The combination of increased TYMS expression (tandem repeat x3) and reduced function of MTHFR (homozygous for the 677T allele) was associated with increased risk of MTX-induced hematologic toxicity but not plasma MTX concentrations [ 71 ]. Only two out of 14 studies found an association between SNPs in TYMS and MTX elimination [ 42 , 81 ].…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Taylor

Vang

López-López

et al. 2021

Cancers

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Methotrexate (MTX) is a mainstay therapeutic agent administered at high doses for the treatment of pediatric and adult malignancies, such as acute lymphoblastic leukemia, osteosarcoma, and lymphoma. Despite the vast evidence for clinical efficacy, high-dose MTX displays significant inter-individual pharmacokinetic variability. Delayed MTX clearance can lead to prolonged, elevated exposure, causing increased risks for nephrotoxicity, mucositis, seizures, and neutropenia. Numerous pharmacogenetic studies have investigated the effects of several genes and polymorphisms on MTX clearance in an attempt to better understand the pharmacokinetic variability and improve patient outcomes. To date, several genes and polymorphisms that affect MTX clearance have been identified. However, evidence for select genes have conflicting results or lack the necessary replication and validation needed to confirm their effects on MTX clearance. Therefore, we performed a systematic review to identify and then summarize the pharmacogenetic factors that influence high-dose MTX pharmacokinetics in pediatric malignancies. Using the PRISMA guidelines, we analyzed 58 articles and 24 different genes that were associated with transporter pharmacology or the folate transport pathway. We conclude that there is only one gene that reliably demonstrates an effect on MTX pharmacokinetics: SLCO1B1.

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“…[14] Previous clinical studies have shown that TYMS polymorphisms are associated with various of cancers, such as gastric cancer, [14] lung cancer, [17] hepatocellular carcinoma, [18] and acute lymphoblastic leukemia. [19] Additionally, TYMS polymorphisms may predict the chemosensitivity to 5-fluorouracil, doxorubicin, cyclophosphamide, pemetrexed and so on. [20,21,9] TYMS SNPs influence cancer susceptibility and chemosensitivity via effects on TYMS expression [22] and its effects differ with respect to race.…”

Section: Discussionmentioning

confidence: 99%

“…Rs2790 is in linkage disequilibrium with a functional SNP (TSER, three or two repeats of a 28-bp sequence) in TYMS [14]and modulates TYMS expression by its effects on the binding of hsa-miR-1248 to its target gene. [19] However, little is known about the functionality of these two SNPs. More experimental studies are urgently needed to clarify the mechanism underlying the effects of TYMS polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

Associations between polymorphisms at microRNA-binding sites in TYMS and breast cancer risk among Chinese women

Wang¹,

Yao²,

Zheng³

et al. 2020

Preprint

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Studies have suggested that thymidylate (TYMS) polymorphisms are associated with breast cancer. However, inconsistent results were obtained and data from Asian populations are largely lacking. In this study, the relationships between two common TYMS polymorphisms (rs2790 and rs1059394) and the breast cancer risk were evaluated. We also studied the TYMS expression between tumor and para-carcinoma tissues, and the association between TYMS levels and prognosis of breast cancer. This hospital-based study included 434 patients and 450 cancer-free individuals. Genotying was performed using Sequenom Mass-ARRAY. The microarray dataset GSE115144 was downloaded to compare the differences in TYMS expression between tumor and para-carcinoma tissues. The microarray dataset GSE20685 was used to analysis the metastasis free survival (MFS) and overall survival (OS) of patients. The rs2790 polymorphism was related to a higher risk of breast cancer (recessive model: OR=1.50, 95%CI=1.02-2.21, P=0.038) and the C allele of rs1059394 was overrepresented in patients with tumor stage III-IV (heterozygote model: OR=0.60, 95%CI=0.39-0.94, P=0.025; dominant model: OR=0.59, 95%CI=0.39-0.89, P=0.013). The tumor tissues had a higher TYMS expression levels and patients with higher TYMS expression levels had worse OS. Overall, TYMS polymorphism may increase susceptibility to breast cancer in Chinese Han women and TYMS expression levels may be a predictive factor for breast cancer patients.

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Genotype and allele frequencies of TYMS rs2790 A > G polymorphism in a Chinese paediatric population with acute lymphoblastic leukaemia

Cited by 4 publications

References 20 publications

3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis

3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Associations between polymorphisms at microRNA-binding sites in TYMS and breast cancer risk among Chinese women

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