374P - Association of CYP1A1 A4889G and T6235C Polymorphisms With Increased Risk and Aggressiveness of Breast Cancer

Abstract

ABSTRACT Background Estrogen and its metabolites, activated by cytochrome P450 enzymes (CYP1A1), participate in the origin and progression of breast cancer (BC). The CYP1A1 gene is highly polymorphic in humans. G and C variant alleles of CYP1A1 A4889G and T6235C polymorphisms encode enzymes with increased activity in activation of these compounds than the respective wild alleles. This study aimed to clarify the biological characteristics of the above-mentioned polymorphisms and their roles in the risk of BC. Materials and methods CYP1A1 A4889G and T6235C genotypes of 742 BC 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. The differences between groups were analyzed by the χ2 test. Power of analysis (PA) was used to determine the effect of sample size on the results obtained in the study. Results Patient and control samples were in Hardy-Weinberg 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; PA= 93.0%). Carriers of the variant G allele were under a 1.50-fold (95% CI: 1.14-1.97) increased risk for BC than those with the wild AA genotype. CYP1A1 4889AG + GG (80.1% versus 19.9%, P= 0.01; PA= 99.0%) and 6235TC + CC (81.4% versus 18.6%, P= 0.02; PA= 99.0%) genotypes were more frequent in BC patients with histological grade III tumors when compared with those with grades I + II tumors. The CYP1A1 4889AG + GG genotypes was also more common in BC patients with histological grade III tumors than in controls (80.1% versus 23.2%; P= 0.04; PA= 72.0%). Carriers of the variant G allele were under a 1.35-fold (95% CI: 1.01-1.82) increased risk of occurrence of histological grade III tumors than others. Conclusion Our data suggest that CYP1A1 A4889G and T6235C polymorphisms alter the risk and aggressiveness of BC in Brazilian women. We believe that women with variant alleles of the above-mentioned genes should receive additional medical attention for disease prevention and early diagnosis. Disclosure All authors have declared no conflicts of interest.