Growth factor, cytokine, and vitamin D receptor polymorphisms and risk of benign prostatic hyperplasia in a community-based cohort of men

Abstract

Objectives To investigate the associations between benign prostatic hyperplasia (BPH) and polymorphisms in genes that encode growth factors, cytokines, and vitamin D and their receptors. Methods A total of 510 white men (median age 60 years) randomly selected from the Olmsted County, Minnesota community participated in a study of BPH from 1990 to 2000. Biennial measurements were made to assess the International Prostate Symptom Score, peak urinary flow rate, and prostate volume. Genotyping of genes that encode transforming growth factor, interleukin-10, tumor necrosis factor, and vitamin D receptor, among others, was performed. Results The CC genotype of the transforming growth factor-beta 1 gene was inversely associated with treatment for BPH (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.15 to 0.98). The presence of at least one allele with 17 or more CA repeats of the epidermal growth factor receptor gene was positively associated with an International Prostate Symptom Score greater than 7 (HR 1.32, 95% CI 1.01 to 1.73). The AA genotype of tumor necrosis factor-alpha was inversely associated with peak urinary flow rate (HR 0.33, 95% CI 0.12 to 0.90). For the vitamin D receptor gene, positive associations were found between prostate volume and the CC genotype of the T_C (Taq 1) polymorphism (HR 1.39, 95% CI 1.0 to 1.92) and the AA genotype of the G_A (Bsm 1) polymorphism (HR 1.36, 95% CI 1.06 to 1.74). Conclusions These findings suggest that transforming growth factor-beta 1, tumor necrosis factor-alpha, epidermal growth factor receptor, and vitamin D receptor polymorphisms may be involved in the pathogenesis of BPH.