Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy.
Clin Cancer Res
; 22(6): 1395-402, 2016 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-26463708
ABSTRACT
PURPOSE:
Aromatase inhibitors can exert unfavorable effects on lipid profiles; however, previous studies have reported inconsistent results. We describe the association of single-nucleotide polymorphisms (SNP) in candidate genes with lipid profiles in women treated with adjuvant aromatase inhibitors. EXPERIMENTALDESIGN:
We conducted a prospective observational study to test the associations between SNPs in candidate genes in estrogen signaling and aromatase inhibitor metabolism pathways with fasting lipid profiles during the first 3 months of aromatase inhibitor therapy in postmenopausal women with early breast cancer randomized to adjuvant letrozole or exemestane. We performed genetic association analysis and multivariable linear regressions using dominant, recessive, and additive models.RESULTS:
A total of 303 women had complete genetic and lipid data and were evaluable for analysis. In letrozole-treated patients, SNPs in CYP19A1, including rs4646, rs10046, rs700518, rs749292, rs2289106, rs3759811, and rs4775936 were significantly associated with decreases in triglycerides by 20.2 mg/dL and 39.3 mg/dL (P < 0.00053), respectively, and with variable changes in high-density lipoprotein (HDL-C) from decreases by 4.2 mg/dL to increases by 9.8 mg/dL (P < 0.00053).CONCLUSIONS:
Variants in CYP19A1 are associated with decreases in triglycerides and variable changes in HDL-C in postmenopausal women on adjuvant aromatase inhibitors. Future studies are needed to validate these findings, and to identify breast cancer survivors who are at higher risk for cardiovascular disease with aromatase inhibitor therapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
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Breast Neoplasms
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Antineoplastic Agents, Hormonal
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Aromatase Inhibitors
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Lipid Metabolism
Type of study:
Clinical_trials
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2016
Document type:
Article