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SNP (Single Nucleotide Polymorphism) marker related to bone marrow suppression of taxane chemotherapy drugs and application of SNP marker

A chemotherapeutic drug and bone marrow suppression technology, applied in the field of SNP markers, can solve the problems of inapplicability to Han patients and inaccurate clinical drug guidance for Chinese Han population, so as to quickly and accurately grasp the patient's condition, improve efficacy and safety, and improve prognostic effect

Inactive Publication Date: 2019-04-26
济南市第四人民医院
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  • Abstract
  • Description
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Problems solved by technology

The distribution of some polymorphic sites in different races is different, and most of the previous studies were done in the Caucasian population, because the gene frequencies of the two races are not exactly the same, the findings may not be applicable to Han patients , cannot be accurately used to guide clinical medication in the Chinese Han population, and the results of previous myelosuppression studies need to be further verified in the Chinese Han population

Method used

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  • SNP (Single Nucleotide Polymorphism) marker related to bone marrow suppression of taxane chemotherapy drugs and application of SNP marker
  • SNP (Single Nucleotide Polymorphism) marker related to bone marrow suppression of taxane chemotherapy drugs and application of SNP marker
  • SNP (Single Nucleotide Polymorphism) marker related to bone marrow suppression of taxane chemotherapy drugs and application of SNP marker

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Experimental program
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Effect test

Embodiment 1

[0041] This embodiment is the collection of samples and the arrangement of sample data.

[0042] Table 2 Comparison of clinical characteristics between the ADR group and the control group

[0043]

[0044]

[0045] From 2012 to 2015, the inventor collected a large number of blood samples from cancer patients from the Fourth People's Hospital of Jinan City, and selected 124 samples that met the following criteria by sorting out the sample data: (1) aged between 18 and 80 years old (2) No major organ dysfunction, blood routine, liver and kidney function, and heart function were basically normal before the first chemotherapy; (3) All patients received at least one cycle of chemotherapy based on paclitaxel or docetaxel; (4) ) Except for patients with bone metastases, all patients had a baseline absolute neutrophil count greater than 1.5×10 9 / L; (5) Baseline information such as age, gender, height, weight, tumor type, and tumor stage of the patient; (6) Detailed information...

Embodiment 2

[0048] This embodiment is the peripheral blood DNA extraction, genotype detection and result analysis. The specific steps are:

[0049] 1. Use the QIAamp DNA Mini Kit to extract DNA from peripheral blood according to the instructions, add 20ul of QIAGEN Protease (or proteinase K) solution to the bottom of a 1.5ml centrifuge tube, extract 200μl of fresh blood and add it to the centrifuge tube;

[0050] 2. Add 200μl Buffer AL, shake for 15s, and bathe in 56℃ water for 10min;

[0051] 3. Centrifuge for a short time to remove the liquid along the inner edge of the centrifuge tube cover;

[0052] 4. Add 200 μl ethanol (96% to 100%), shake for 15 seconds, and centrifuge for a short time to remove the liquid along the inner edge of the centrifuge tube cover;

[0053] 5. Add the mixture obtained above (including the precipitate) into the QIAamp spin column, put the spin column into a 2ml collection tube, close the cap of the centrifuge tube, centrifuge at 6000×g (8000rpm) for 1min, ...

Embodiment 3

[0075] In order to further verify the effect of the above SNPs on taxane-related leukopenia or neutropenia, an association analysis was performed on patients with severe leukopenia or neutropenia. The results showed that SLC15A1rs2297322 and HNF4αrs6130615 were significantly associated with myelosuppression. SLC15A1rs2297322 was associated with increased risk of both leukopenia and neutropenia (REC, OR=2.933, 95% CI: 1.017-8.464, p=0.047; REC, OR=3.549, 95% CI: 1.290-9.763, p=0.014). HNF4α rs6130615 was significantly associated with increased risk of leukopenia (REC, OR=2.933, 95% CI: 1.017-8.464, p=0.047). In two association analyses, rs2297322 and rs6130615 were identified as susceptibility loci for taxane-associated myelosuppression.

[0076] Thus, the combination of rs2297322 and rs6130615 could well differentiate cancer patients prone to varying degrees of myelosuppression.

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Abstract

The invention belongs to the field of genetic engineering and oncology and discloses an SNP (Single Nucleotide Polymorphism) marker related to bone marrow suppression of taxane chemotherapy drugs andapplication of the SNP marker. The marker is either rs2297322 of a gene SLC15A1 or rs6130615 of a gene HNF4alpha. As the application of the SNP marker, the invention further provides a diagnostic kitfor detecting or forecasting the bone marrow suppression of the taxane chemotherapy drugs. A biological marker for clinically preventing taxane related bone marrow suppression at an early stage is provided, meanwhile, the kit is provided for clinically forecasting the chemotherapy effect of the taxane drugs at an early stage, and thus, the realization of precise medication of taxane is promoted.

Description

technical field [0001] The invention belongs to the field of genetic engineering and oncology, and relates to a SNP marker related to bone marrow suppression of taxane chemotherapeutic drugs and application thereof. Background technique [0002] Taxanes, including paclitaxel and docetaxel, are widely used in the standard treatment of a variety of solid tumors, such as breast, ovarian, pancreatic, gastric, non-small cell lung, and head and neck cancers. Paclitaxel can promote the formation of cellular microtubules and prevent their physiological depolymerization, inhibit the rapid division of cancer cells and thus inhibit tumor growth. However, taxanes often cause adverse drug reactions during cancer treatment, such as myelosuppression, peripheral neuropathy, and gastrointestinal toxicity. In particular, myelosuppression occurs in approximately 80% of taxane-treated patients and is one of the main reasons for discontinuation of taxane therapy. [0003] Myelosuppression refe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/106C12Q2600/156
Inventor 郭亮苏克莉郝桂君周晨希
Owner 济南市第四人民医院
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