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GSTM1 and GSTT1 polymorphisms associated with pain in a chemotherapy-induced peripheral neuropathy cohort.
- Source :
-
Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2023 Aug; Vol. 149 (10), pp. 7405-7412. Date of Electronic Publication: 2023 Mar 20. - Publication Year :
- 2023
-
Abstract
- Purpose: Chemotherapy induced peripheral neuropathy (CIPN) is a debilitating condition that is a direct consequence of receiving cancer treatment. The molecular aetiology of CIPN is not well understood, and it is theorised that there may be a genetic component. Genetic polymorphisms in Glutathione-S Transferase (GST) genes, including GSTT1, GSTM1 and GSTP1, encode for enzymes known to metabolise drugs used in chemotherapy, and have been theorised to be associated with CIPN. This study aimed to investigate four markers in these genes for an association in a mixed cancer cohort in relation to CIPN (n = 172).<br />Methods: CIPN was measured using the neuropathy item from the Patient Reported Outcome Common Terminology Criteria for Adverse Event (PRO-CTCAE) assessment. Genotyping for all samples was performed using PCR for the GSTM1 and GSTT1 null variants and restriction fragment length polymorphisms for the GSTP1 and GSTM1 polymorphisms.<br />Results: No associations were found for the GST gene markers in relation to CIPN within our study, or CIPN severity. Longitudinal stratification of the CIPN phenotypes to examine links for neuropathy, identified nominally significant protective associations with the GSTM* null allele (p-value = 0.038, OR = 0.55) and the presence of pain at month 2 of treatment, as well as a risk factor for pain related month 2 of treatment for individuals with the GSTT1*null allele (p-value = 0.030, OR = 1.64). Higher severity of pain in patients with CIPN persisted at each time-point compared to those without CIPN.<br />Conclusion: No significant results for an association between CIPN with polymorphisms in GSTM1, GSTT1 and GSTP1 were identified. However, associations for the GSTM1¬-null and GSTT1-null polymorphisms with pain at month 2 following chemotherapy were identified.<br /> (© 2023. The Author(s).)
- Subjects :
- Humans
Genetic Predisposition to Disease
Case-Control Studies
Polymorphism, Genetic
Glutathione Transferase genetics
Glutathione S-Transferase pi genetics
Risk Factors
Pain drug therapy
Pain genetics
Genotype
Peripheral Nervous System Diseases chemically induced
Peripheral Nervous System Diseases genetics
Antineoplastic Agents
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1335
- Volume :
- 149
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of cancer research and clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 36939926
- Full Text :
- https://doi.org/10.1007/s00432-023-04677-3