GENETICS OF BREAST CANCER AND HORMONE REPLACEMENT THERAPY

Background The major known risk] actors,for female breast cancer are associated with prolonged exposure to increased levels of oestrogen. The predominant theory suggests that enhanced cell proliferation, induced either by endogenous or exogenous oestrogens, increases the number of cell divisions and thereby the possibility for mutation. However, current evidence also supports a role for oxidative metabolites, in particular catechol oestrogens in the initiation of breast cancer. There is a considerable inter-individual variability in the metabolic pathways of both. oestrogen and catechol oestrogens which are attributed to polymorphisms in the genes encoding,for the respective enzymes. In this paper the potential role of polymorphic genes encoding for enzymes involved in oestrogen biosynthesis (CYP17 CYP19, 17 beta-HSD) and conversion of the oestrogen metabolites and their by-products (COMT, CYP1A1, CYP1B1, GSTs, MnSOD) in modulating individual susceptibility to breast cancer are reviewed Information about polymorphisms in these genes is becoming important to determine the risk and benefits of hormone replacement therapy (HRT). Conclusions The, findings of pharmacogenomic studies about polymorphisms in oestrogen synthesizing and metabolizing genes could have an important clinical value: before prescribing HRT, we would offer women genetic counselling and define their genotype. T hits, we would be able to organize an individualized postmenopausal period for each woman accordingly.