Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy

Cesar Santa-Maria, Amanda Blackford, Anne T. Nguyen, Todd C. Skaar, Santosh Philips, Steffi Oesterreich, James M. Rae, Zeruesenay Desta, Jason Robarge, Norah Lynn Henry, Anna M. Storniolo, Daniel F. Hayes, Roger S Blumenthal, Pamela Ouyang, Wendy S Post, David A. Flockhart, Vered Stearns

Research output: Contribution to journalArticle

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. Experimental Design: 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 associatedwith 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. Clin Cancer Res; 22(6); 1395-402.

Original languageEnglish (US)
Pages (from-to)1395-1402
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2016

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Aromatase Inhibitors
letrozole
Breast Neoplasms
Lipids
Genes
Single Nucleotide Polymorphism
exemestane
Triglycerides
Therapeutics
HDL Lipoproteins
Observational Studies
Survivors
Linear Models
Fasting
Estrogens
Research Design
Cardiovascular Diseases
Prospective Studies
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy. / Santa-Maria, Cesar; Blackford, Amanda; Nguyen, Anne T.; Skaar, Todd C.; Philips, Santosh; Oesterreich, Steffi; Rae, James M.; Desta, Zeruesenay; Robarge, Jason; Henry, Norah Lynn; Storniolo, Anna M.; Hayes, Daniel F.; Blumenthal, Roger S; Ouyang, Pamela; Post, Wendy S; Flockhart, David A.; Stearns, Vered.

In: Clinical Cancer Research, Vol. 22, No. 6, 15.03.2016, p. 1395-1402.

Research output: Contribution to journalArticle

Santa-Maria, C, Blackford, A, Nguyen, AT, Skaar, TC, Philips, S, Oesterreich, S, Rae, JM, Desta, Z, Robarge, J, Henry, NL, Storniolo, AM, Hayes, DF, Blumenthal, RS, Ouyang, P, Post, WS, Flockhart, DA & Stearns, V 2016, 'Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy', Clinical Cancer Research, vol. 22, no. 6, pp. 1395-1402. https://doi.org/10.1158/1078-0432.CCR-15-1213
Santa-Maria, Cesar ; Blackford, Amanda ; Nguyen, Anne T. ; Skaar, Todd C. ; Philips, Santosh ; Oesterreich, Steffi ; Rae, James M. ; Desta, Zeruesenay ; Robarge, Jason ; Henry, Norah Lynn ; Storniolo, Anna M. ; Hayes, Daniel F. ; Blumenthal, Roger S ; Ouyang, Pamela ; Post, Wendy S ; Flockhart, David A. ; Stearns, Vered. / Association of variants in candidate genes with lipid profiles in women with early breast cancer on adjuvant aromatase inhibitor therapy. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 6. pp. 1395-1402.
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AU - Santa-Maria, Cesar

AU - Blackford, Amanda

AU - Nguyen, Anne T.

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AU - Philips, Santosh

AU - Oesterreich, Steffi

AU - Rae, James M.

AU - Desta, Zeruesenay

AU - Robarge, Jason

AU - Henry, Norah Lynn

AU - Storniolo, Anna M.

AU - Hayes, Daniel F.

AU - Blumenthal, Roger S

AU - Ouyang, Pamela

AU - Post, Wendy S

AU - Flockhart, David A.

AU - Stearns, Vered

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N2 - 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. Experimental Design: 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 associatedwith 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. Clin Cancer Res; 22(6); 1395-402.

AB - 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. Experimental Design: 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 associatedwith 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. Clin Cancer Res; 22(6); 1395-402.

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