Plasma levels of nitrate and risk of prostate cancer: a prospective study
Wu T, Wang Y, Ho SM, Giovannucci E. Cancer Epidemiol Biomarkers Prev. 2013 May 15. [Epub ahead of print]


Environmental Health, University of Cincinnati Medical Center.


Background: Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer. Previous small, cross-sectional studies reported positive associations between circulating nitrate/nitrite levels and cancer. Prospective studies examining the association between plasma nitrate and cancer, especially prostate cancer (PCa), are lacking. Methods:We conducted a nested case-control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of PCa were identified from 1997-2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls. Results:We have found that baseline levels of plasma nitrate were not associated with risk of PCa. Compared to quintile 1, the relative risk from quintiles 2-5 were 1.13 (95% CI 0.78-1.63), 0.93 (95% CI 0.63-1.38), 0.95 (95% CI 0.65-1.39), and 0.99 (95% CI 0.68-1.48); p for trend was 0.9 after adjustment of multivariate risk factors. Further, plasma nitrate appeared to be inversely associated with advanced-stage PCa. The relative risk across extreme quartiles was 0.44 (95% CI 0.17-1.12; p for trend = 0.07) for the whole data set and 0.30 (95% CI 0.09-0.99; p for trend = 0.05) for the fasting data set. Conclusions:We did not find an increased risk of PCa associated with higher plasma nitrate levels. A potential protective association between nitrate and aggressive forms of PCa requires confirmation. Impact:Nitrate-nitrite-nitric oxide pathway has emerged as a new therapeutic pathway for chronic diseases. The results of this study certainly merit replications.