CYP1A1*2A polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI and its combined effects with EGFR intron 1 (CA)n polymorphism

摘要: Abstract Background Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of efficacy for EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms EGFR and cytochrome P450, family 1, member A1 (CYP1A1) genes were associated with clinical outcome NSCLC patients treated EGFR-TKI. Methods Genotypes intron 1 (CA)n repeat R497K gene *2A (3801 T → C) *2C (2455 A → G) CYP1A1 evaluated 115 by PCR-RFLP DNA sequencing. Genetic correlated outcomes EGFR-TKIs. From a subgroup whose tumour tissues available, associations between somatic mutations, expression, genomic also analysed. Results CYP1A1*2A independent predictive factors ( p  = 0.046, = 0.011, respectively) latter was prognostic = 0.001) observed strong synergistic effect from two genotypes. Specifically, both T/T allele shorter CA repeats (⩽16 CA) showed an improved response = 0.002) compared T/C or C/C longer (both alleles >16 CA). In contrast, CYP1A1*2C, no relationship EGFR-TKIs p =  0.573; = 0.629, respectively). Both SNPs correlation mutations. Conclusions The findings this study suggest that polymorphism is predictor EGFR-TKI therapy, combining analysis may be useful predicting treatment