| Summary: | Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of <i>GSTM1</i> and <i>GSTT1</i> null polymorphisms, <i>CYP1B1</i> Val432Leu and <i>MTHFR</i> C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with <i>GSTT1</i> null genotype and with both <i>GSTM1</i> and <i>GSTT1</i> null genotypes were 50 years old or more at the diagnosis (<i>p</i>-value = 0.021 and 0.018, respectively). Older women with <i>GSTM1</i> null genotype were also carriers of the <i>CYP1B1</i>Val allele (<i>p</i>-value = 0.012). As well, <i>GSTT1</i> null and <i>CYP1B1</i>Val genotypes were correlated with diagnosis at later ages (<i>p</i>-value = 0.022). Similar results were found associating <i>MTHFR</i> C677T and <i>GSTT1</i> null polymorphism (<i>p</i>-value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.
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