Vitamin D receptor gene Bsml polymorphism correlates with erbB-2/HER-2 expression in human rectal cancer

Apart from the regulation of calcium metabolism, 1,25-dihydroxyvitamin D-3 plays an essential role in cell proliferation and differentiation in severa l tissues. The vitamin D receptor (VDR) gene shows polymorphisms in humans that appear to be clinically significant in some pathological conditions. I n the present study, the Bsml polymorphism of the VDR gene was studied in 5 9 Caucasian patients with rectal cancer (mean follow-up: 48 months). The re lationship between VDR genotypes and the expression of oncogenes as well as their influence on survival were also investigated. VDR polymorphism was e xamined in tumor and normal mucosa cells by PCR technique. The expression o f erbB-2/HER-2, p53, ras and epidermal growth factor receptor (EGFR) was al so detected by immunohistochemistry and protein blotting. The presence of t he VDR B allele significantly correlated with the overexpression of the erb B-2 oncogene. There was no difference in the VDR genotype between cancer an d normal mucosal cells. Coexpression of erbB-2, pan-ras, p53 and EGFR inter nal and external domains was significantly higher in cancer cells than in n ormal mucosa. There was no significant correlation between VDR genotypes an d age, gender, tumor infiltration depth, number and site of lymph node meta stases and lymphatic or blood vessel infiltration. The VDR genotype alone d id not influence survival. Overexpression of erbB-2 and EGFR was associated with a poor prognosis. In patients expressing only one oncogene in cancer cells, the presence of the VDR B allele showed a tendency to a poor prognos is. in conclusion, VDR gene Bsml polymorphism might affect the development and prognosis of rectal cancer by influencing erbB-2 oncogene expression. C opyright (C) 2000 S. Karger AG, Basel.