Breast Cancer Association with CYP1A2 Activity and Gene Polymorphisms - a Preliminary Case-control Study in Tunisia

The aim of the present study was to evaluate the relative contribution of CYP1A2 isoforms (-3860 G/A,-2467T/delT and -163C/A) in control subjects and breast cancer patients to the metabolism of caffeine in humanliver. Restriction fragment length polymorphism analysis of PCR-amplified Fragments (PCR-RFLP) was usedfor the genotyping of CYP1A2 SNPs and HPLC allowed the phenotyping through the measurement of CYP1A2activity using the 17X + 13X + 37X/137X urinary metabolite ratio (CMR) and plasma caffeine half life (T1/2).The CYP1A2 -3860A genotype was associated with a decreased risk of breast cancer. In contrast, distributionsof the CYP1A2 -2467T/delT or -2467delT/delT and -163A/C or A/A genotypes among breast cancer patients andcontrols were similar. When the genotype and phenotype relationship was measured by comparing the meanCMR ratios and caffeine half life within the genotype groups between subjects and breast cancer patients, therewere no significant differences except for -3860 A, most of them being homozygous for the -3860 G/G SNP andhad a significant higher mean CMR ratio and half life than those with -3860 G/A (P=0.02). The results of thispreliminary study show a significant association between CP1A2 -3860 G variant and CYP1A2 phenotype whichmust be confirmed by further large-size case-control studies.