Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial
| Autor: | Elma Meershoek-Klein Kranenbarg, Hans Gelderblom, Danny Houtsma, Hein Putter, Renee Baak-Pablo, Cornelis J.H. van de Velde, Caroline Seynaeve, D.B.Y. Fontein, Johan W. R. Nortier, Henk-Jan Guchelaar, Tahar van der Straaten |
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| Přispěvatelé: | Medical Oncology |
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Cancer Research Exemestane chemistry.chemical_compound Breast cancer Risk Factors Genotype Odds Ratio Medicine Aromatase Netherlands Aged 80 and over biology Middle Aged Combined Modality Therapy Postmenopause Treatment Outcome Aromatase inhibitors Female Adult medicine.medical_specialty medicine.drug_class Single-nucleotide polymorphism Breast Neoplasms Polymorphism Single Nucleotide Cyp19 SDG 3 - Good Health and Well-being Internal medicine Humans Germ-Line Mutation Aged Neoplasm Staging Gynecology Aromatase inhibitor business.industry Odds ratio medicine.disease Pharmacotherapy chemistry Pharmacogenetics Adverse events biology.protein Neoplasm Grading business |
| Zdroj: | Breast Cancer Research and Treatment, 144(3), 599-606 Breast Cancer Research and Treatment, 144(3), 599-606. Springer New York |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | Musculoskeletal adverse events (MSAEs) and vasomotor symptoms (VMSs) are known side-effects of aromatase inhibitors, and may be related to genetic variations of the aromatase gene (CYP19A1). We investigated the relationship between these specific AEs and single nucleotide polymorphisms (SNPs) in the CYP19A1 gene in postmenopausal, hormone receptor-positive early breast cancer (BC) patients treated with adjuvant exemestane for 5 years. Dutch patients who were randomized to receive 5 years of exemestane in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. A tagging-SNP approach was performed, covering 80 % of variations of the CYP19A1 gene with 30 SNPs. Logistic regression analyses were used to assess the risk of reporting VMSs or MSAEs in relation to genotypes within selected SNPs. Of 737 included patients, 281 patients reported at least one MSAE (n = 210) or VMS (n = 163). Homozygous AA genotype of rs934635 was associated with a significantly higher odds of MSAEs (multivariate odds ratio (OR) 4.66, p = 0.008) and VMSs (multivariate OR 2.78, p = 0.044). Regarding both rs1694189 and rs7176005, the homozygous variant genotypes (TT) were associated with a higher odds of VMSs, but not MSAEs (OR 1.758, p = 0.025 and OR 6.361, p = 0.021, respectively). Our exploratory analysis demonstrated that some CYP19A1 gene variations may be associated with MSAEs and/or VMSs. Specifically, patients with the homozygous variant rs934635 genotype reported more MSAEs and VMSs. Although further confirmatory studies are warranted, genomic profiling can help identify patients at an increased risk of reporting these specific AEs, potentiating further personalized BC treatment. |
| Databáze: | OpenAIRE |
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