Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with aromatase inhibitor associated bone loss in women with ER + breast cancer

Bone. 2013 Aug;55(2):309-14. doi: 10.1016/j.bone.2013.04.021. Epub 2013 May 1.


Purpose: Polymorphisms in the CYP19A1 (aromatase) gene have been reported to influence disease-free survival and the incidence of musculoskeletal complaints in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancer. Bone loss and fractures are well-recognized complications from AI therapy. The objective of this study is to determine the influence of polymorphisms in the CYP19A1 gene on bone loss among patients taking aromatase inhibitors for ER+ breast cancer.

Patients and methods: The subjects consisted of 97 postmenopausal women with ER+ breast cancer who were initiated on third-generation AIs. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and at 6 and 12 months. Twenty-four hour urine N-telopeptide (NTX) was measured by Elisa and serum estradiol was measured by ultrasensitive radioimmunoassay at baseline, and at 6 months. Genotyping was done by Taqman SNP allelic discrimination assay.

Results: Women with the AA genotype for the rs700518 (G/A at Val(80)) developed significant bone loss at the lumbar spine and the total hip at 12 months relative to patients carrying the G allele (GA/GG); both p = 0.03. There was a borderline greater increase in urinary NTX in those with the AA genotype compared to patients with the G allele, p = 0.05; but no significant difference in changes in estradiol levels among the genotypes.

Conclusion: Patients with the AA genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for AI-associated bone loss and deserve close follow-up during long-term AI therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Aged, 80 and over
  • Aromatase / genetics*
  • Aromatase Inhibitors / adverse effects*
  • Bone Density / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Collagen Type I / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Middle Aged
  • Osteoporosis / chemically induced
  • Osteoporosis / genetics*
  • Peptides / blood
  • Polymorphism, Single Nucleotide*
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics


  • Aromatase Inhibitors
  • Collagen Type I
  • Peptides
  • Receptors, Estrogen
  • collagen type I trimeric cross-linked peptide
  • Aromatase
  • CYP19A1 protein, human