Linkage of angiotensin I-converting enzyme gene insertion/deletion polymorphism to the progression of human prostate cancer.

Angiotensin-converting enzyme (ACE) degrades vasodilator kinins and generates angiotensin II (Ang II). It has been reported that ACE is synthesized by the prostate and that the AT-1 receptor subtype is the predominant prostatic Ang II receptor. A polymorphism in the human ACE gene has been described and the highest levels of circulating and tissue ACE activity are found in carriers of the DD genotype. In the present study, ACE genotypes were determined in 170 patients with prostate cancer and their association with disease progression was analysed. It was found that the DD genotype was present in 31 of 78 (39.8%) patients with advanced disease and in 19 of 82 (23.2%) with localized disease: this difference was statistically significant (OR = 2.18, 95% CI = 1.11-4.03; p = 0.024). Step-wise logistic regression analysis was used to identify predictive parameters of advanced disease and it was observed that the DD genotype (p = 0.002, OR = 5.4, 95% CI = 1.84-16.06), high-grade tumour (p < 0.001, OR = 8.04, 95% CI = 3.03-21.33), and high serum PSA (p < 0.001, OR = 10.87, 95% CI = 4.06-29.13) were significantly associated with advanced disease. The results of this study support the hypothesis that genetic factors related to ACE may influence the behaviour of human prostate cancer. Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.