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The number of reports investigating disease susceptibility based on the carriage of low-penetrance, high-frequency single nucleotide polymorphisms (SNPs) has increased over the last years. Evidence is accumulating defining specific individual variations in breast cancer susceptibility. Genetic variations of the estradiol and xenobiotic metabolisms, as well as genes involved in cell cycle control, have been described as significant contributors to breast cancer susceptibility with variations depending on ethnic background and co-factors such as smoking and family history of breast cancer. In sum, the highest level of evidence to date linking SNPs and breast cancer comes from nested case-control studies within the prospective Nurses' Health Study. These data establish seven SNPs – hPRB +331 G/A, AR CAG repeat, CYP 19 TTTA(10), CYP 1A1 Msp I, VDR FOK1, XRCC1 Arg194Trp, and XRCC2 Arg188His – as small, but significant risk factors for spontaneous, non-hereditary breast cancer. In addition, meta-analysis of data in the literature established the TGFBR1*6A, the HRAS1, GSTP Ile105Val, and the GSTM1 SNPs as low-penetrance genetic risk factors for sporadic breast cancer. The clinical consequences of such a risk elevation may be a detailed instruction of the patient as to general measures of breast cancer prevention such as a low-fat diet, optimization of the BMI, physical exercise, avoidance of alcohol and long-term hormone replacement therapy (HRT), and participation in a breast cancer screening program between the age of 50 and 70 years. Specific surgical or drug interventions such as prophylactic mastectomy and oophorectomy or prophylactic intake of tamoxifen are not indicated based on SNP analysis at this time.

laboratoriumsmedizin

How valid is single nucleotide polymorphism (SNP) diagnosis for the individual risk assessment of breast cancer? / Welchen Stellenwert hat der diagnostische Einsatz von Einzelnukleotid-Polymorphismen (SNPs) bei der individuellen Risikoeinschätzung von Brustkrebs?