Association of genetic polymorphisms in CYP19 and CYP1A1 with the oestrogen receptor-positive breast cancer risk

Eur J Cancer. 2003 Nov;39(17):2531-7. doi: 10.1016/j.ejca.2003.08.017.


Since tamoxifen has been shown to reduce the risk of oestrogen receptor (ER)-positive, but not ER-negative, breast cancers in a chemoprevention trial (P-1), it is important to develop assays to assess risk factors for ER-positive breast cancer in order to appropriately select candidates for chemoprevention with tamoxifen. Thus, the significance of genetic polymorphisms of genes involved in oestrogen biosynthesis (CYP19) and metabolism (CYP1A1) as a risk factor for ER-positive breast cancers was evaluated. A case-control study was conducted with 257 breast cancer patients and 191 healthy female controls. Two polymorphisms, CYP19 (TTTA repeats) in intron 4 and CYP1A1 6235C/T in the 3' non-coding region, and their association with the breast cancer risk after adjustment for the other epidemiological risk factors were examined. CYP19 (TTTA)7(-3bp) allele carriers showed a significantly (P<0.05) increased risk of ER-positive breast cancers (Odds Ratio (OR)=1.72, 95% Confidence Interval (CI) 1.10-2.69), but not ER-negative breast cancers. CYP1A1 6235C allele carriers showed a non-significant (P=0.06) trend towards a decreased risk of ER-positive breast cancers (OR=0.65, 95% CI 0.42-1.02), but not ER-negative breast cancers. The combination of these two polymorphisms was found to be more useful in the assessment of the ER-positive breast cancer risk (OR=3.00, 95% CI=1.56-5.74) than the CYP19 (TTTA)7(-3bp) polymorphism alone. The combination of CYP19 (TTTA)7(-3bp) and CYP1A1 6235C/T polymorphisms is associated with an ER-positive, but not ER-negative, breast cancer risk, and, thus, would be useful in the selection of candidates for chemoprevention with tamoxifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aromatase / genetics*
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Cytochrome P-450 CYP1A1 / genetics*
  • Estrogens / blood
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Receptors, Estrogen / genetics*
  • Risk Factors


  • Estrogens
  • Receptors, Estrogen
  • Aromatase
  • Cytochrome P-450 CYP1A1