GENETICS OF BREAST CANCER AND HORMONE REPLACEMENT THERAPY
Abstract
BACKGROUND The major known risk factors for female breast cancer are associated with prolongedexposure to increased levels of oestrogen. The predominant theory suggests that enhancedcell proliferation, induced either by endogenous or exogenous oestrogens, increasesthe number of cell divisions and thereby the possibility for mutation. However, currentevidence also supports a role for oxidative metabolites, in particular catechol oestrogens,in the initiation of breast cancer. There is a considerable inter-individual variability inthe metabolic pathways of both oestrogen and catechol oestrogens which are attributedto polymorphisms in the genes encoding for the respective enzymes. In this paper thepotential role of polymorphic genes encoding for enzymes involved in oestrogen biosynthesis (CYP17, CYP19, 17ß-HSD) and conversion of the oestrogen metabolites and theirby-products (COMT, CYP1A1, CYP1B1, GSTs, MnSOD) in modulating individual susceptibility to breast cancer are reviewed. Information about polymorphisms in these genes isbecoming important to determine the risk and benefits of hormone replacement therapy(HRT). CONCLUSIONS The findings of pharmacogenomic studies about polymorphisms in oestrogen synthesizingand metabolizing genes could have an important clinical value: before prescribing HRT,we would offer women genetic counselling and define their genotype. Thus, we would beable to organize an individualized postmenopausal period for each woman accordinglyDownloads
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