{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:19Z","timestamp":1772150419040,"version":"3.50.1"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009530","name":"Jawaharlal Institute Of Postgraduate Medical Education and Research","doi-asserted-by":"publisher","award":["Edn.7(1)\/2010dt21.02.2011"],"award-info":[{"award-number":["Edn.7(1)\/2010dt21.02.2011"]}],"id":[{"id":"10.13039\/501100009530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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<jats:italic>TCL1A<\/jats:italic>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<jats:italic>TCL1A<\/jats:italic>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<jats:italic>rs11849538 (G)<\/jats:italic>, with an allele frequency of about 27.3%, followed by<jats:italic>rs7158782-G<\/jats:italic>(27.3%),<jats:italic>rs7159713-G<\/jats:italic>(25.8%), and<jats:italic>rs2369049-G<\/jats:italic>(22.5%). The genetic association analysis indicated no significant difference in the proportion of<jats:italic>TCL1A<\/jats:italic>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<jats:italic>rs7158782<\/jats:italic>, suggesting a potential biological function. Our findings suggest that<jats:italic>TCL1A<\/jats:italic>gene polymorphisms may not play any role in the prediction of letrozole-induced AEs in South Indian HR+ breast cancer patients.<\/jats:p>","DOI":"10.1371\/journal.pone.0247989","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T17:38:42Z","timestamp":1616607522000},"page":"e0247989","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-9159","authenticated-orcid":true,"given":"Gurusamy","family":"Umamaheswaran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dharanipragada","family":"Kadambari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh Kumar","family":"Muthuvel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveena A. N.","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biswajit","family":"Dubashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Aibor Dkhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrasekaran","family":"Adithan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"pone.0247989.ref001","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2165\/00002018-200528100-00003","article-title":"Clarification of terminology in drug safety","volume":"28","author":"JK Aronson","year":"2005","journal-title":"Drug Saf"},{"key":"pone.0247989.ref002","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0165-6147(00)01717-X","article-title":"Genetic 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