Geontype-phenotype correlations applied for clinical genetics of cancer are finally achieving a dream level.

It is exemplified in a very particular way in chemoprevention, surveillance and chemotherapy directed to BRCA1 mutation carriers. Females with such constitutional abnormalities have initial breast/ovarian cancer risk around 80% during lifetime. According to our latest data it is possible to correlate genotypes, serum selenium level and cancer risk among BRCA1 carriers with very high statistical significance and power. These data strongly suggest that optimization of selenium amount in diet might reduce the risk of breast/ovarian cancer at least three times in around 80% of BRCA1 carriers who should keep serum selenium level around 60-80?g/l and in around 20% carriers with distinct genotype in whom serum selenium level should be above 80 ?g/l. This situation can not be taken as a standard procedure, however even today it is a very attractive option especially that a very low proportion of potential adverse events can be expected due to regulation of selenium level in the body.

Another spectacular progress has been developed in chemotherapy. Existing data are maintaining results of pilot studies indicating the ratio of complete pathologic responses (PCR) at the level above 80% for neo-adjuvant treatment of breast cancers among BRCA1 carriers. Until now, the frequency of PCR among unselected breast cancer patients treated before mastectomy was only 2,5%, thus we can observe the milestone progress. It is especially impressive, that it was achieved with cisplatin which is not a new drug but generic being in clinical use since more than 30 years.

Efficiency of cisplatin treatment for BRCA1 dependant cancers was observed also for disseminated breast cancers showing around 80% of remissions. Finally, there are suggestions that malignances of any site can show increased frequency of remissions provided they occurred in BRCA1 carriers and are treated with cisplatin.

In summary, these two above mentioned examples are showing in extremely spectacular way the value of genotype - clinical correlations and enormous progress in oncology which can be achieved as a result of it.

It can be expected that this type of correlation will be find also for additional groups of individuals with high inherited predisposition to cancer or other disorders.

At present, we should be as much determinate as possible to diagnose as soon as possible all of BRCA1 carriers and to provide them appropriate prevention, surveillance and treatment.

Prof. dr hab. med. Jan Lubiński