TY - JOUR
T1 - Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer
AU - Umamaheswaran, Gurusamy
AU - Kadambari, Dharanipragada
AU - Muthuvel, Suresh Kumar
AU - Kumar, Naveena A.N.
AU - Dubashi, Biswajit
AU - Dkhar, Steven Aibor
AU - Adithan, Chandrasekaran
N1 - Funding Information:
The work was funded by JIPMER intramural research Grant (No. End.7(1)/2010 dated 21.02.2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder provided support in the form of research materials for authors (UG and DK), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.
Publisher Copyright:
© 2021 Umamaheswaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/3
Y1 - 2021/3
N2 - 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 letrozoleinduced AEs. The study subjects were postmenopausal HR+ breast cancer patients who were receiving adjuvant letrozole. Genomic DNA was isolated by a routine standard phenolchloroform 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.
AB - 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 letrozoleinduced AEs. The study subjects were postmenopausal HR+ breast cancer patients who were receiving adjuvant letrozole. Genomic DNA was isolated by a routine standard phenolchloroform 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.
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U2 - 10.1371/journal.pone.0247989
DO - 10.1371/journal.pone.0247989
M3 - Article
C2 - 33760860
AN - SCOPUS:85103310378
SN - 1932-6203
VL - 16
JO - PLoS One
JF - PLoS One
IS - 3 March
M1 - e0247989
ER -
