ECTS2014 Poster Presentations Genetics (11 abstracts)
Genetic determinants of bone mineral density loss in aromatase inhibitors treatment in the B-ABLE Cohort
Maria Rodriguez-Sanz 1 , Natalia Garcia-Giralt 1 , Elisa Torres-del Pliego 1, , Daniel Prieto-Alhambra 1, , Sonia Servitja 4 , Susana Balcells 5 , Leonardo Mellibovsky 1, , Daniel Grinberg 5 , Ignasi Tusquets 4 , Adolfo Diez-Perez 1, & Xavier Nogués 1,
1IMIM (Hospital del Mar Medical Research Institute), Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III FEDER, Barcelona, Spain; 2Internal Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain; 3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; 4Medical Oncology Department, IMIM (Hospital del Mar Research Institute), Barcelona, Spain; 5Departament de Genètica, Universitat de Barcelona, IBUB, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain.
Bone density (BMD) loss is a consequence of aromatase inhibitors (AI) treatment of breast cancer. B-ABLE cohort includes 391 postmenopausal women with early breast cancer starting AI therapy. Participants experienced a 1.98% (95% CI 1.54–2.42% P<0.0001) bone loss at lumbar spine (LS) and 1.24% (95% CI 0.81–1.67% P<0.0001) bone loss at femoral neck (FN) after 1 year on AI therapy and a 3.51% (95% CI 3.00–4.03% P<0.0001) bone loss at LS and 2.07% (95% CI 1.51–2.63% P<0.0001) bone loss at FN after 2 years. We aim to identify genetic variants associated with BMD loss during AI therapy.
Single nucleotide polymorphisms (SNPs) in genes involved in vitamin D and estrogen pathways were genotyped in the B-ABLE cohort. Multivariate linear regression was performed to test the association between SNPs and LS and FN BMD loss after 1 and 2 years of follow-up. All models were adjusted for age, BMI, tamoxifen, chemotherapy, 25(OH)-VITD and type of AI. P<0.05 was considered nominally significant.
Two SNPs in CYP11A1 (rs2959008 and rs7174179) were associated with FN BMD loss at 1 (P=0.003 and P=0.012) and 2 years (P=0.004 and P=0.002). For LS BMD loss, SNPs in HSD3B2 (rs2854964), CYP2C19 (rs12248560) and CYP2C9 (rs28371674) were associated at 1 year of follow-up (P=0.026, P=0.019 and P=0.011 respectively). The rs12248560 remained significant at 2 years (P=0.014).
The rs11907350 in CYP24A1 was associated with FN BMD loss at 1 year. For LS BMD loss, one SNP in GC (rs11907350) at 1 year (P=0.020) and one in VDR (rs2544037) at 2 years (P=0.024) reached significant P-values. Only the rs7174179 in CYP11A1 for FN BMD loss association at 2 years remained significant after Bonferroni correction.
Conclusion: Several genes in estrogen and vitamin D signaling appeared involved in BMD loss in AI-treated women, suggesting a complex regulation of this outcome.
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Bone Abstracts
ISSN 2052-1219 (online)
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