PMID- 33760860
OWN - NLM
STAT- MEDLINE
DCOM- 20211012
LR  - 20211012
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 3
DP  - 2021
TI  - Polymorphisms of T- cell leukemia 1A gene loci are not related to the development 
      of adjuvant letrozole-induced adverse events in breast cancer.
PG  - e0247989
LID - 10.1371/journal.pone.0247989 [doi]
LID - e0247989
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 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.
FAU - Umamaheswaran, Gurusamy
AU  - Umamaheswaran G
AUID- ORCID: 0000-0002-8709-9159
AD  - Department of Pharmacology, Centre for Advanced Research in Pharmacogenomics, 
      Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), 
      Puducherry, India.
FAU - Kadambari, Dharanipragada
AU  - Kadambari D
AD  - Departments of Surgery and Medical Education, Jawaharlal Institute of 
      Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
FAU - Muthuvel, Suresh Kumar
AU  - Muthuvel SK
AD  - Center for Bioinformatics, School of Life Sciences, Pondicherry University, 
      Puducherry, India.
FAU - Kumar, Naveena A N
AU  - Kumar NAN
AD  - Departments of Surgery and Medical Education, Jawaharlal Institute of 
      Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
FAU - Dubashi, Biswajit
AU  - Dubashi B
AD  - Department of Medical Oncology, Regional Cancer Center, Jawaharlal Institute of 
      Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
FAU - Aibor Dkhar, Steven
AU  - Aibor Dkhar S
AD  - Department of Pharmacology, Centre for Advanced Research in Pharmacogenomics, 
      Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), 
      Puducherry, India.
FAU - Adithan, Chandrasekaran
AU  - Adithan C
AD  - Department of Pharmacology, Centre for Advanced Research in Pharmacogenomics, 
      Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), 
      Puducherry, India.
AD  - Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical 
      Education and Research (JIPMER), Puducherry, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210324
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (TCL1A protein, human)
RN  - 7LKK855W8I (Letrozole)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Antineoplastic Agents/*adverse effects
MH  - Breast Neoplasms/drug therapy/*genetics/pathology
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Loci
MH  - Genotype
MH  - Humans
MH  - Letrozole/*adverse effects
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins/*genetics
PMC - PMC7990231
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/03/25 06:00
MHDA- 2021/10/13 06:00
PMCR- 2021/03/24
CRDT- 2021/03/24 17:26
PHST- 2020/09/05 00:00 [received]
PHST- 2021/02/17 00:00 [accepted]
PHST- 2021/03/24 17:26 [entrez]
PHST- 2021/03/25 06:00 [pubmed]
PHST- 2021/10/13 06:00 [medline]
PHST- 2021/03/24 00:00 [pmc-release]
AID - PONE-D-20-27959 [pii]
AID - 10.1371/journal.pone.0247989 [doi]
PST - epublish
SO  - PLoS One. 2021 Mar 24;16(3):e0247989. doi: 10.1371/journal.pone.0247989. 
      eCollection 2021.