SNP markers related to hand-foot syndrome and application thereof

A technology of hand-foot syndrome and markers, applied in the fields of genetic engineering and oncology medicine, can solve the problems of lack of genome-wide research and verification, limitations, etc.

Inactive Publication Date: 2019-11-19
SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current research on capecitabine-induced hand-foot syndrome is mostly based on candidate gene studies of enzyme-encoding genes in the capecitabine metabolic pathway. related research and verification

Method used

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  • SNP markers related to hand-foot syndrome and application thereof
  • SNP markers related to hand-foot syndrome and application thereof
  • SNP markers related to hand-foot syndrome and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] The collection of embodiment 1 sample and the collation of data

[0089] From 2008 to 2018, a large number of blood samples were collected from the biobank of Cancer Hospital Affiliated to Sun Yat-sen University. After sorting out the sample information, 1104 samples that met the following criteria were selected for genome-wide microarray scanning and single SNP Taqman genotyping :

[0090] 1. Selection of research samples

[0091] Inclusion criteria:

[0092] (1) Colorectal cancer patients with clear pathological diagnosis and clinical stage;

[0093] (2) The expected survival is greater than 6 months;

[0094] (3) Functional status score (KPS) ≥ 70 points;

[0095] (4) aged 18 to 80 years old;

[0096] (5) Have complete medical records (medical history, physical examination, related examinations, previous treatments);

[0097] (6) Patients are treated with chemotherapy regimens containing capecitabine;

[0098] (7) Participate voluntarily and sign the informed ...

Embodiment 2

[0119] TaqMan genotyping detection of embodiment 2 single SNP

[0120] The loci rs2853741 and rs1890775 associated with hand-foot syndrome found in Example 1 through genome-wide scanning were detected in an independent verification population, including 590 patients with colorectal cancer, including 181 cases of severe hand-foot syndrome (grade≥ 2) colorectal cancer patients, and 409 colorectal cancer patients with no or mild hand-foot syndrome (grade≤1). Then use Taqman (Applied Biosystems) genotyping to detect these samples, the specific steps are:

[0121] (1) Collect 3mL of peripheral venous blood with an EDTA anticoagulant tube, centrifuge at 3500r / min for 10 minutes, and then suck out the plasma;

[0122] (2) Remove red blood cells: add an equal volume of red blood cell lysate (10mmol / L Tris pH7.6; 5mmol / L MgCl 2 ; 10mmol / L NaCl), mix well by upside down, centrifuge at 4000r / min for 10 minutes, discard the supernatant, then add 5mL red blood cell lysate, mix well by tu...

Embodiment 3

[0138] Example 3 Construction and verification of hand-foot syndrome risk score model induced by the tumor chemotherapy drug capecitabine in patients with colorectal cancer

[0139] Further, we incorporated the significantly related loci rs2853741 and rs1890775 found in Example 1 and obtained in Example 2 into the construction of the hand-foot syndrome risk score model, and found that this combination can well distinguish mild (HFS grade≤1) and severe (HFS grade≥2) colorectal cancer patients with hand-foot syndrome.

[0140] The 514 patients in Example 1 were used as a training set to perform multivariate logistic regression, and the regression coefficient β was substituted into the formula to construct a hand-foot syndrome risk model. The correlation coefficient results of logistic regression are shown in Table 3.

[0141] The risk score formula is:

[0142] Risk score=(0.7588×rs2853741 type score)+(-0.5382×rs1890775 type score);

[0143] Wherein, the scoring of typing: fo...

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Abstract

The invention discloses SNP markers related to hand-foot syndrome and application thereof, and specific amplification primers and specific probes for detecting the marker. The SNP markers are rs2853741 and rs1890775, the nucleotide sequences of the specific amplification primers are respectively shown as SEQ ID NO.1-4, and the nucleotide sequences of the specific probes are respectively shown as SEQ ID NO.5-8. The SNP markers provided by the invention have high specificity and sensitivity, and can well predict the susceptibility for treating the hand-foot syndrome of a patient to by using a tumor chemotherapeutic drug capecitabine. The SNP markers, the amplification primers and a related kit can be used for evaluating the risk and the severity of hand-foot syndrome of the patient, can adopt protective measures in advance aiming at high-risk patients, is beneficial to realizing individualized treatment for the patient, is beneficial to the treatment of the patient and improves the lifequality of the patient.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering and tumor medicine. More specifically, it relates to a SNP marker related to hand-foot syndrome and its application. Background technique [0002] Capecitabine is a 5-FU prodrug widely used in the treatment of gastrointestinal malignancies and breast malignancies. glycoside, and then metabolized to 5' deoxyfluorouridine by cytidine deaminase in liver and tumor tissue, and finally metabolized to 5-FU by thymidine phosphorylase in tumor tissue, 5-FU mainly inhibits thymidylate synthesis 80% to 90% of 5-FU is finally catabolized by dihydropyrimidine dehydrogenase. [0003] Common adverse reactions of capecitabine are hand-foot syndrome (HFS), digestive system symptoms, bone marrow suppression, nervous system symptoms, cardiotoxicity, hyperbilirubinemia, fatigue, etc., and other systemic symptoms (such as alopecia, Allergic reactions, abnormal pigmentation), etc. Among them, the highes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/156C12Q2600/106
Inventor 贾卫华董思岐王曈旻
Owner SUN YAT SEN UNIV
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