Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer

Letrozole, an aromatase inhibitor (AI), is the first-line adjuvant drug for treating hormone receptor-positive (HR+) breast cancer in postmenopausal women. However, harmful adverse events (AEs) and significant differences in drug response among individuals remain a significant problem in clinical ap...

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Bibliographic Details
Published in:PloS one 2021-03, Vol.16 (3), p.e0247989-e0247989
Main Authors: Umamaheswaran, Gurusamy, Kadambari, Dharanipragada, Muthuvel, Suresh Kumar, Kumar, Naveena A N, Dubashi, Biswajit, Aibor Dkhar, Steven, Adithan, Chandrasekaran
Format: Article
Language:English
Subjects:
Adverse and side effects
Bioinformatics
Biology and Life Sciences
Breast cancer
Cancer
Cancer therapies
Chemotherapy
Clinical outcomes
Deoxyribonucleic acid
Departments
DNA
Drug therapy
Drugs
Editing
Education
Ethnicity
Gene loci
Gene polymorphism
Genetic aspects
Genotype & phenotype
Graduate studies
Health aspects
Leukemia
Medical education
Medical research
Medicine and Health Sciences
Menopause
Minority & ethnic groups
Oncology, Experimental
Patients
Pharmacogenomics
Pharmacology
Post-menopause
Side effects
Single nucleotide polymorphisms
Surgery
T cells
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Summary:Letrozole, an aromatase inhibitor (AI), is the first-line adjuvant drug for treating hormone receptor-positive (HR+) breast cancer in postmenopausal women. However, harmful adverse events (AEs) and significant differences in drug response among individuals remain a significant problem in clinical application. Current evidence suggests that the observed individual variation in the treatment outcomes of AI is conferred by genetic variants. Hence, in this study, we examined the association of TCL1A gene polymorphisms with letrozole-induced AEs. The study subjects were postmenopausal HR+ breast cancer patients who were receiving adjuvant letrozole. Genomic DNA was isolated by a routine standard phenol-chloroform method. In total, 198 South Indian patients were genotyped for four single nucleotide polymorphisms (SNPs) in the TCL1A gene loci by the TaqMan allelic discrimination assay using the RT-PCR system. We used the odds ratio and 95% confidence interval to assess the genetic association. Musculoskeletal (MS) AEs and vasomotor symptoms (VMSs) are the most common side effects observed in the study cohort. Among 198 patients, 81 experienced musculoskeletal toxicity, reporting MS-AEs, 57 had VMSs, and 33 of them had both. The most frequently identified polymorphic variants in the patient series were rs11849538 (G), with an allele frequency of about 27.3%, followed by rs7158782-G (27.3%), rs7159713-G (25.8%), and rs2369049-G (22.5%). The genetic association analysis indicated no significant difference in the proportion of TCL1A gene variants between patients with and without AEs on either MS-AEs or VMSs. Though we observed high LD in all patient groups, the inferred haplotypes displayed a non-significant association with letrozole-induced specific AEs. However, the SNP functionality analysis by RegulomeDB provided a 2b rank score for rs7158782, suggesting a potential biological function. Our findings suggest that TCL1A gene polymorphisms may not play any role in the prediction of letrozole-induced AEs in South Indian HR+ breast cancer patients.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0247989