The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer

Yousef, Al-Motassem; Zawiah, Mohammed; Al-Yacoub, Shorouq; Kadi, Taha; Tantawi, Dua’ a; Al-Ramadhani, Hanguin

doi:10.1007/s00280-018-3608-6

“…But this study focused on colorectal cancer and the sample size was small. The relationship between rs1805087 and the efficacy of 5-FU in gastric cancer patients remains to be explored 15 .…”

Section: Introductionmentioning

confidence: 99%

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Huang,

Yan,

Huang

et al. 2024

JoVE

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Gastric cancer is a common heterogeneous tumor. Most patients have advanced gastric cancer at the time of diagnosis and often need chemotherapy. Although 5-fluorouracil (5-FU) is widely used for treatment, its therapeutic sensitivity and drug tolerance still need to be determined, which emphasizes the importance of individualized administration. Pharmacogenetics can guide the clinical implementation of individualized treatment. Single nucleotide polymorphisms (SNPs), as a genetic marker, contribute to the selection of appropriate chemotherapy regimens and dosages. Some SNPs are associated with folate metabolism, the therapeutic target of 5-FU. Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133, dihydrofolate reductase (DHFR) rs1650697 and rs442767, methionine synthase (MTR) rs1805087, gamma-glutamyl hydrolase (GGH) rs11545078 and solute carrier family 19 member 1 (SLC19A1) rs1051298 have been investigated in different kinds of cancers and antifolate antitumor drugs, which have potential forecasting and guiding significance for application of 5-FU. The ion torrent next-generation semiconductor sequencing technology can rapidly detect gastric cancer-related SNPs. Each time a base is extended in a DNA chain, an H + will be released, causing local pH changes. The ionic sensor detects pH changes and converts chemical signals into digital signals, achieving sequencing by synthesis. This technique has low sample requirement, simple operation, low cost, and fast sequencing speed, which is beneficial for guiding individualized chemotherapy by SNPs.

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“…Samples containing 50 uL DNA were quantified using a NanoDrop 2000 UV spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA). A total of 13 SNPs in 7 genes involved in capecitabine PD were selected based on their prevalence in the European population and previous research in the scientific literature [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 40 ] ( Table 4 ).…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, apart from TYMS , the genes involved in the folate cycle and DNA repair pathways play an important role in the PD of capecitabine ( Figure 1 ) [ 8 ]. Indeed, numerous studies have investigated the impact of several SNPs in genes related to capecitabine’s PD, such as TYMS , enolase superfamily member 1 gene ( ENOSF1 ), methylenetetrahydrofolate reductase gene ( MTHFR ), ERCC excision repair 1, endonuclease non-catalytic subunit gene ( ERCC1 ), ERCC excision repair 2, TFIIH core complex helicase subunit gene ( ERCC2 ), X-ray repair cross-complementing 1 gene ( XRCC1 ), and X-ray repair cross-complementing 3 gene ( XRCC3 ) on the effectiveness of FP therapy in gastrointestinal neoplasms [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. However, the available evidence remains limited and characterized by conflicting findings, necessitating further investigation and exploration.…”

Section: Introductionmentioning

confidence: 99%

Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer

Cura,

Sánchez-Martín,

Márquez-Pete

et al. 2023

IJMS

0

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Colorectal cancer (CRC) is a highly prevalent form of neoplasm worldwide. Capecitabine, an oral antimetabolite, is widely used for CRC treatment; however, there exists substantial variation in individual therapy response. This may be due to genetic variations in genes involved in capecitabine pharmacodynamics (PD). In this study, we investigated the role of single-nucleotide polymorphisms (SNPs) related to capecitabine’s PD on disease-free survival (DFS) in CRC patients under adjuvant treatment. Thirteen SNPs in the TYMS, ENOSF1, MTHFR, ERCC1/2, and XRCC1/3 genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan® probes. A significant association was found between favorable DFS and the ENOSF1 rs2612091-T allele (p = 0.010; HR = 0.34; 95% CI = 0.14–0.83), as well as with the TYMS/ENOSF1 region ACT haplotype (p = 0.012; HR = 0.37; 95% CI = 0.17–0.80). Other factors such as low histological grade (p = 0.009; HR = 0.34; 95% CI = 0.14–0.79) and a family history of cancer (p = 0.040; HR = 0.48; 95% CI = 0.23–0.99) were also linked to improved DFS. Therefore, the SNP ENOSF1 rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens.

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“…But this study focused on colorectal cancer and the sample size was small. The relationship between rs1805087 and the efficacy of 5-FU in gastric cancer patients remains to be explored 15 .…”

Section: Introductionmentioning

confidence: 99%

JoVE Video Dataset

0

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Gastric cancer is a common heterogeneous tumor. Most patients have advanced gastric cancer at the time of diagnosis and often need chemotherapy. Although 5-fluorouracil (5-FU) is widely used for treatment, its therapeutic sensitivity and drug tolerance still need to be determined, which emphasizes the importance of individualized administration. Pharmacogenetics can guide the clinical implementation of individualized treatment. Single nucleotide polymorphisms (SNPs), as a genetic marker, contribute to the selection of appropriate chemotherapy regimens and dosages. Some SNPs are associated with folate metabolism, the therapeutic target of 5-FU. Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133, dihydrofolate reductase (DHFR) rs1650697 and rs442767, methionine synthase (MTR) rs1805087, gamma-glutamyl hydrolase (GGH) rs11545078 and solute carrier family 19 member 1 (SLC19A1) rs1051298 have been investigated in different kinds of cancers and antifolate antitumor drugs, which have potential forecasting and guiding significance for application of 5-FU. The ion torrent next-generation semiconductor sequencing technology can rapidly detect gastric cancer-related SNPs. Each time a base is extended in a DNA chain, an H + will be released, causing local pH changes. The ionic sensor detects pH changes and converts chemical signals into digital signals, achieving sequencing by synthesis. This technique has low sample requirement, simple operation, low cost, and fast sequencing speed, which is beneficial for guiding individualized chemotherapy by SNPs.

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The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer

Abstract: Genetic polymorphism in DPYD seems to be associated with DFS in CRC patients receiving an adjuvant regimen of 5-FU/capecitabine-based chemotherapy. Further studies are needed to verify these findings.

Cited by 10 publications

References 28 publications

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer

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