Single nucleotide polymorphisms: impact on susceptibility to chemotherapy in patients with colorectal cancer
Creators: name: Vaz-Salgado, M. Angeles
name: Albarran, Victor
name: Pozas, Javier
name: Ferreiro, Reyes
name: Pachón, Vanessa
name: Longo, Federico
name: Rodriguez, Mercedes
name: Barreto, Emma
name: Earl, Julie
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Science Policy
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Computational Biology

description: Single-nucleotide polymorphisms (SNPs) in enzyme-coding genes play a role in susceptibility to anti-cancer therapy. A prospective study was performed of the relationship between enzyme activity and treatment response, drug toxicity and hypersensitivity reactions in 51 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. SNP analysis was performed in 22 enzyme-coding genes with a previously described role in treatment efficacy. SLC6 and MTHR enzyme activity was related with rates of progressive disease, GSTP1 activity with anti-EGFR antibodies-related skin toxicity, CYP3A5 and MTHR with chemotherapy dose reduction, CYP2B6, IL10, MTHR and TYMS activity with the risk of drug hypersensitivity reactions. Pharmacogenetics is a valuable predictive marker in oncology, related to chemotherapy treatment response, toxicity and hypersensitivity. This study looked at specific changes in 22 genes from 51 people with colorectal cancer, who were treated with a type of chemotherapy and targeted cancer drugs. These gene changes, called SNPs, affected how certain enzymes work in the body. Changes in the SLC6 and MTHR genes were linked to faster cancer growth. The GSTP1 gene was connected to skin rashes caused by one of the cancer drugs. Some patients needed lower doses of chemotherapy due to changes in the CYP3A5 and MTHR genes, while other changes increased the chance of allergic reactions to the treatment. These gene changes can help doctors predict how patients will respond to treatment and what side effects they might experience. Single-nucleotide polymorphisms (SNPs) in enzyme-coding genes affect susceptibility to anti-cancer therapy.Normal SLC6 and MTHR activity was related with higher rates of treatment failure (progressive disease).Bevacizumab-related hypertension was related with decreased GSTM3 activity.Normal GSTP1 activity was associated with anti-EGFR antibodies-related skin toxicity.CYP3A5 and MTHR intermediate activity was related with the need for chemotherapy dose reduction.Normal CYP2B6 activity, intermediate or decreased IL10 activity, intermediate MTHR activity, and intermediate TYMS activity were related with a higher risk of drug hypersensitivity reactions.SNPs in enzyme-coding genes play a role in the individual susceptibility to chemotherapy and toxicity in patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy.SNPs in enzyme-coding genes also influence the risk of hypersensitivity reactions.Pharmacogenetic analysis identifies predictive markers in oncological patients. Single-nucleotide polymorphisms (SNPs) in enzyme-coding genes affect susceptibility to anti-cancer therapy. Normal SLC6 and MTHR activity was related with higher rates of treatment failure (progressive disease). Bevacizumab-related hypertension was related with decreased GSTM3 activity. Normal GSTP1 activity was associated with anti-EGFR antibodies-related skin toxicity. CYP3A5 and MTHR intermediate activity was related with the need for chemotherapy dose reduction. Normal CYP2B6 activity, intermediate or decreased IL10 activity, intermediate MTHR activity, and intermediate TYMS activity were related with a higher risk of drug hypersensitivity reactions. SNPs in enzyme-coding genes play a role in the individual susceptibility to chemotherapy and toxicity in patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. SNPs in enzyme-coding genes also influence the risk of hypersensitivity reactions. Pharmacogenetic analysis identifies predictive markers in oncological patients.