VITAMIN-D-RECEPTOR GENE POLYMORPHISM IS ASSOCIATED WITH METASTATIC BREAST-CANCER

The vitamin D receptor (VDR) has been detected in breast tumor cells. We tested the hypothesis that VDR gene polymorphism might influence th e outcome of women affected by breast cancer. A total of 88 breast can cer patients were recruited: 50 women were affected by newly diagnosed breast cancer whereas 38 women suffered from relapsing disease. The i ndividual genetic pattern for VDR was evaluated by DNA extraction foll owed by PCR amplification of the VDR gene, and digestion with the rest riction enzyme BsmI. In 167 healthy women, participating in the osteop orosis prevention trial and being used as a control, we detected 121 B b heterozygotes (72%), 26 homozygotes for the bb alleles (16%), and 20 homozygotes for the BE alleles (12%). In the newly diagnosed breast c ancer group the occurrence of Bb patients was 58% (29/50); bb patients represented 22% (11/50), and BE cases were 20% (10/50). The VDR frequ ency distribution in the control and primary disease patient groups wa s not statistically different. In the metastatic cancer group, the pre valence of the bb genotype (14/38; 37%) was double the percentage of c ontrol subjects, whereas the percentage of BE women with metastases wa s half the control group (2/38; 5%). Women who were homozygous bb appe ared to have almost a four times higher risk of developing metastases than BE women. Whatever the molecular mechanisms underlying the VDR ef fects in cancer cells, we believe that the VDR gene polymorphism may r epresent an important determinant in the evaluation of women affected by breast cancer and might help design targeted therapy.