Association of CYP1A1 A4889G and T6235C polymorphisms with the risk of breast cancer in Brazilian women.

Abstract

e11551 Background: Estrogen, activated by cytochrome P450 enzymes (CYP1A1), participates in the breast cancer (BC) development. G and C variant alleles of CYP1A1 A4889G and T6235C polymorphisms encode enzymes with increased activity in activation of this compound when compared with the respective wild alleles. This study aimed to clarify the roles of the polymorphisms in the risk of BC. Methods: CYP1A1 A4889G and T6235C genotypes of 742 sporadic breast cancer (SBC) patients (median age: 52 years, 638 Caucasians, 104 non-Caucasians) and 742 healthy women (median age: 40 years, 638 Caucasians, 104 non-Caucasians) were obtained in genomic DNA by PCR and enzymatic digestion. Results: Patient’s and control’s samples were in HW equilibrium at CYP1A1 A4889G (χ2= 0.15, P= 0.70; χ2= 1.15, P= 0.28) and T6235C (χ2= 2.65, P= 0.10; χ2= 1.93, P= 0.16) loci. The frequency of CYP1A1 4889AG+GG genotypes was higher in patients than in controls (29.0% versus 23.2%, P= 0.004). Carriers of the G allele were under a 1.50 (95% CI: 1.14-1.97)-fold increased risk for SBC than those with the wild AA genotype. The frequencies of 4889AG+GG genotypes in Caucasian SBC patients were higher than those found in Non-Caucasian (30.4% vs 20.2%, P= 0.03), and also in controls (30.4% vs 23.2%, P= 0.002). Carriers of G allele were under a 1.61 (95% CI: 1.20-2.15)-fold increased risk for SBC than others. A higher frequency of the CYP1A1 4889AG+GG genotypes was also seen in patients with an earlier median age at first full-term pregnancy (FFTP), compared to those who had the first pregnancy with a later medium age (33.8% vs 26.1%, P=0.03), and also when compared to controls (33.8% vs 23.2%, P= 0.001). Women with the CYP1A1 4889AG+GG genotypes and with earlier FFTP were under a 1.87 (95% CI: 1.32-2.67)-fold increased risk for SBC than others. The CYP1A1 6235CC genotype was more common in pre-obese or obese SBC patients than in underweight or normal SBC patients (6.8% vs 4.0%, P= 0.04). Conclusions: Our data suggest that CYP1A1 A4889G and T6235C polymorphisms alter BC risk in Brazilian women. We believe that women with variant alleles of the referred polymorphisms should receive additional medical attention for disease prevention and early diagnosis.