Abstract LB-403: Levels of nitric oxide and prostate cancer development in healthy US men enrolled in the Health Professionals Follow-up Study

Abstract

Abstract Nitric oxide (NO) has a strong impact on cancer development. Experimental studies have reported that, depending on levels, NO has either tumoricidal or tumor-promoting effects. In addition, NO is strongly associated with oxidative and inflammatory pathways, which have been implicated in prostate cancer. In general, maintaining normal-range levels of NO is important for physiological function and may actually have tumoricidal effects. Furthermore, extremely high levels of NO have been found to stimulate prostate tumor growth in rats. However, the relationship between plasma NO level and risk of prostate cancer (PCa) development has not been assessed. NO is difficult to measure directly in large epidemiologic studies. This barrier has hampered the identification of NO-related pathways in cancer development. We have found that plasma levels of nitrite/nitrate, measured as a surrogate marker of NO, are both stable and reproducible within individuals over time. Using a prospective nested case-control design, we identified 600 PCa cases and 600 matched controls from 2000-2004 among men who provided a blood sample in 1993-1995. This study is nested within a blood cohort in the Health Professionals Follow-up Study. We have already measured baseline plasma levels of nitrite/nitrate in 170 cases and 170 controls. The multivariate-adjusted odds ratio of nitrite/nitrate from quintile 2-quintile 4 as compared to quintile 1 are 0.71 (95%CI, 0.24-2.75), 0.20 (95%CI, 0.05-0.75), 0.81 (95%CI, 0.30-2.91), and 1.12 (95%CI, 0.65-2.78), respectively. Our preliminary data suggest that medium levels of nitrite/nitrate maximally reduce the risk of prostate cancer, and that men with high or low levels of nitrite/nitrate may be at elevated risk of prostate cancer. Confirming our results in our remaining samples and other populations may have important implications for prevention of prostate cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-403.