Outcome in prostate cancer: associations with skin type and polymorphism in pigmentation-related genes

Epidemiological studies have suggested that UV exerts a protective effect o n prostate cancer. Accordingly, we determined, in 210 prostate cancer cases , whether parameters of exposure, skin type and polymorphism in MC1R, VDR a nd TYR were associated with the outcome parameters, histological grade, cli nical stage and presence of bone metastases. We used logistic regression an alysis, with correction for age and metastases, stage and grade in the mode ls, to determine if the frequencies of individual factors were different in the patient groups. The development of metastases was not associated with UV exposure parameters. Paradoxically, patients with skin type 1 were at si gnificantly reduced risk [P = 0.027, odds ratio (OR) 0.17, 95% CI 0.03-0.82 ] of developing metastases compared with cases with skin type 4. MC1R Val92 /Val92 and VDR ff were associated with increased risk of metastases (ORs 4. 30 and 4.98, respectively). Further, cumulative exposure (P = 0.005, OR 0.8 5/year) and increasing proportion of outdoor occupation (P = 0.001, OR 0.84 /unit) were associated with reduced risk of advanced stage tumours. Skin ty pes, MC1R or VDR genotypes were not significantly associated with advanced stage. None of the exposure parameters, skin types or genotypes were associ ated with tumour grade. While MC1R Val92/Val92 and VDR ff were only associa ted with bone metastases, TYR genotypes were associated with each of the ou tcome parameters. Thus, in logistic regression models that included age, bu t not advanced stage and high grade histology, TYR A1A2 was significantly a ssociated with reduced risk of metastases (P = 0.033, OR 0.41). Similarly, in models that included age but not the other outcome parameters, associati ons between TYR A2A2 and high-grade and advanced stage were significant (P = 0.040, OR 0.41) or approached significance (P = 0.052, OR 0.44), respecti vely. These data indicate for the first time that pigmentation response to UV is associated with outcome in prostate cancer.