Abstract
Objective: Investigating the relationship between single nucleotide polymorphisms (SNPs) and the toxic and adverse effects of paclitaxel and platinum-based chemotherapy in patients with malignant tumors, to provide recommendations for individualized treatment. Methods: Determinate 17 patients with malignant tumor DNA site and analysis. Results: 1. All 17 selected specimens’ fluorouracil related genes 18DPYD*2A(476002G>A)GG type、153DPYD*13(1679T>G)TT type 154DPYD(2846A>T)TT type, and the synthesis of DPYD enzyme activity. 21GSTP1(313A>G) polymorphism site mutation rate was 25.0%(4 cases), 29XRCC1(16323944T>C) polymorphism site mutation rate was 90.9%(10 cases), 62ABCB1(3435C>T) polymorphism site mutation rate was 52.9%(9 cases), and 68MTHFR(677C>T) polymorphism site mutation rate was 50.0%(8 cases). 2. Fluorouracil related genes 18DPYD*2A(476002G>A)GG type, 153DPYD*13(1679T>G)TT type, 154DPYD(2846A>T)TT type ,and the synthesis DPYD enzyme activity is normal. 3. Paclitaxel related genes 62ABCB1(3435T>C) CC type has a lower incidence of hematotoxicity and neurotoxicity, than CT type and TT type. 13ABCB1(2677T>G)GG type has a higher rate of drug resistance than TT type. 14CYP1B1*3(C>G)CC type has a higher progression-free survival. Platinum-related genes 21GSTP1(313A>G)AA is homozygous wild type and has a higher incidence of hematotoxicity than GA type. 29XRCC1(1196T>C)CC is homozygous mutant and has a higher risk of serious neutropenia than CT type. 62ABCB1 (3435T>C)CC is homozygous mutant and has a higher risk of lymphatic metastasis than TC type and TT type. 68MTHFR(677C>T)TT type is homozygous mutant and has a higher mucosal toxicity and toxic and side effects than CT type and CC type. Conclusion: Single nucleotide polymorphism is related to the toxic and side effects of chemotherapy，the detection of SNP to predict the toxicity risk of drug users can be an important reference index to guide clinical individualized treatment.
Highlights
The lasted data from the World Health Organization (WHO) shows that malignant tumor has been the second leading cause of death worldwide, killing 8.8 million people in 2015
Single nucleotide polymorphisms (SNPs) mainly refers to DNA sequence polymorphism caused by mutation of single nucleotide at the genome level
About 40% of individuals with low DPYD enzyme activity carry the DPYD*2A allele, and 60% of patients will have grade 4 severe granulocyte reduction after 5-fu treatment
Summary
Investigating the relationship between single nucleotide polymorphisms (SNPs) and the toxic and adverse effects of paclitaxel and platinum-based chemotherapy in patients with malignant tumors, to provide recommendations for individualized treatment. Platinum-related genes 21GSTP1(313A>G)AA is homozygous wild type and has a higher incidence of hematotoxicity than GA type. Conclusion: Single nucleotide polymorphism is related to the toxic and side effects of chemotherapy,the detection of SNP to predict the toxicity risk of drug users can be an important reference index to guide clinical individualized treatment
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