1. ¹Cancer Research UK Cancer Medicine Research Division, University of Leeds, Leeds, UK
2. ²Cancer Research UK Genetic Epidemiology Division, University of Leeds, Leeds, UK
3. ³Institute of Cancer Research, Sutton, Surrey, UK
4. ⁴Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK
5. ⁵Royal Marsden NHS Trust, Sutton, Surrey, UK

Correspondence: RA Eeles, Translational Cancer Genetics Team, Institute of Cancer Research, Sutton, Surrey SM2 5PT, UK. E-mail: Rosalind.Eeles@icr.ac.uk

⁶List available on request.

⁷These authors contributed equally to this work.

Received 1 September 2004; Revised 17 December 2004; Accepted 17 December 2004; Published online 15 February 2005.

Abstract

We investigated the association between seven polymorphisms in four candidate genes involved in vitamin D and androgen metabolism with early-onset prostate cancer (CaP) risk. The polymorphisms were genotyped in 288 UK males who were diagnosed with CaP at the age of 55 y or younger and up to 700 population-based controls. An additional 50 cases (not selected for age) and 76 controls were also genotyped. Short (22 repeats) AR (CAG)_n repeats were associated with a significantly reduced risk of early onset CaP (OR 0.68, 95% CI 0.50–0.91) compared with men with long (>22) repeats. Men homozygous for the leucine variant of SRD5A2 p.89V>L were also found to be at a significantly increased risk of CaP compared with men who were homozygous for the valine allele (OR 1.84, 95% CI 1.15–2.98). No associations were found with the AR (GGC)_n, CYP17 Msp A1 I, VDR Taq I, SRD5A2 (TA)_n and p.49A>T polymorphisms and CaP risk. These findings suggest that common polymorphisms in the AR and SRD5A2 genes may be associated with early-onset CaP in British men.