title: Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Santa-Maria
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Blackford
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nguyen
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Santosh
authors.initials: S
authors.lastname: Philips
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Zeruesenay
authors.initials: Z
authors.lastname: Desta
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jason
authors.initials: J
authors.lastname: Robarge
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Norah Lynn
authors.initials: NL
authors.lastname: Henry
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Storniolo
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland. vstearn1@jhmi.edu.
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D008055:Lipids