Endocrine Abstracts

Prostate and breast cancers remain common causes of cancer related deaths in the UK. The majority of cases appear to be of a multifactorial aetiology that includes a genetic component. It has been suggested that low levels of circulating 1,25 dihydroxyvitamin D₃ are associated with an increased risk of both breast and prostate cancer. A number of polymorphisms in the vitamin D receptor (VDR) gene have been identified resulting in differing genotypes that may alter susceptibility to cancer. We are investigating whether specific polymorphisms (Bsm 1 and Fok 1 ) in the VDR gene are associated with altered breast and metastatic prostate cancer risk in a UK Caucasian population. After receiving approval from the Ethics Board, patients with breast and metastatic prostate cancer were recruited from clinics at St. George's Hospital (breast cancer group n=313, median age=60.35, metastatic prostate cancer group n=58, median age=72.4) and controls for both groups were recruited through the UK National Breast Screening Programme (n=410, median age=55.7). For part of this study high throughput Real-time PCR assays have been optimised for the single nucleotide polymorphisms we are investigating. The Taqman technique, which uses competitive fluorescent hybridisation probes, was used to determine Fok 1 genotype. In addition, the Lightcycler, which involves product-probe hybrid melt curve analysis, was used to determine Bsm 1 genotype. The VDR polymorphism Bsm 1 was significantly associated with increased breast cancer risk; the frequency of the b (at risk) allele was 0.65 in breast cancer patients as opposed to 0.58 in controls. This gave an odds ratio for bb vs BB genotype of 1.79 (95% CI, 1.12-2.86, p=0.0221). Furthermore, Bsm 1 genotyping of several common breast cancer cell lines showed that a very high proportion ( >70%) displayed the bb genotype. The Fok 1 polymorphism was not associated with breast or prostate cancer risk.

This research was funded by the Breast Cancer Campaign and the Prostate Research Campaign, UK.