Endocrine Abstracts (2002) 3 P125

Approaches to evaluating the role of vitamin D receptor polymorphisms in breast and prostatic carcinoma

M Guy, LC Lowe, G Oades, D Bretherton-Watt, JL Mansi & KW Colston

Oncology, Gastroenterology, Endocrinology and Metabolism, St George's Hospital Medical School, London, UK.

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.

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