Study of the genetic basis of Trabecular Bone Score reduction related to aromatase inhibitors

M. Pineda-Moncusí, M. Rodríguez-Sanz, S. Servitja, A. Díez-Pérez, I. Tusquets, X. Nogués, Natalia García-Giralt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

© 2018 Sociedad Espanola de Investigacion Osea y del Metabolismo Mineral (SEIOMM). Objectives: Aromatase inhibitors (AI) are effective adjuvant endocrine therapies for breast cancer patients, although they have been associated with an increased risk of osteoporotic fracture. Trabecular Bone Score (TBS) loss has been previously demonstrated, although it may vary among AI-treated patients. This study aims to identify the genetic basis associated with TBS change by studying steroidogenic pathway genes. Material and methods: The B-ABLE cohort studies prospectively postmenopausal women with breast cancer under treatment with AI. TBS is calculated from the raw data acquired in dual-energy x-ray absorptiometry (DXA) scan at the outset of the study and at the end of AI-treatment. The relative TBS change was calculated as the percentage variation of the TBS value at the end of treatment from baseline. To study the possible genetic association, nucleotide polymorphisms (SNPs) were genotyped in genes CYP11A1, CYP17A1, HDE3B2, HDE17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, GC, CYP27B1, VDR and CYP24A1. The possible relationship between genes and TBS changes was studied by multiple linear regression, considering models of dominant, recessive and additive genetic inheritance. Results: The study included 212 women that had not been treated with bisphosphonates and had available TBS data. Half of the patients had been treated previously with tamoxifen. The percentage of intraindividual TBS change was -0.04% [95% CI: -0.05 to -0.03; p < 0.001] at the end of AI treatment. The SNP rs6013897 in the gene CYP24A1 showed a significant association with TBS reduction [p=0.03565; coefficient β (95% CI) = -1.55 (-2.98 to -0.11)]. Conclusions: The CYP24A1 gene could be involved in the phenotypic variability found in bone microarchitecture deterioration during AI treatment.
Original languageEnglish
Pages (from-to)82-87
JournalRevista de Osteoporosis y Metabolismo Mineral
Volume10
Issue number2
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Aromatase inhibitors
  • Breast cancer
  • Genetic association study
  • TBS

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