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

Abstract

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 6235 C/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 6235 C 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 6235 C/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.