Abstract
It has been suggested that nitrate and nitrite may play a role in the etiology of human oral cancer. We investigated whether salivary nitrate and nitrite and the activity of nitrate reductase (NRase) may affect the risk of oral cancer in Egypt, an area with high levels of environmental nitrosating agents. Levels of salivary nitrite (8.3 ± 1.0 μg/ml) and nitrate (44 ± 3.7 μg/ml) and activity of NRase (74 ± 10 nmol/ml/min) were significantly (P < 0.05) higher in oral cancer patients (n = 42) compared to control Egyptian healthy individuals (n = 40, nitrite = 5.3 ± 0.3 μg/ml, nitrate = 27 ± 1.2 μg/ml, and NRase activity = 46 ± 4 nmol/ml/min). The adjusted odds ratio (OR) and the 95% confidence intervals (C.I.) for risk of oral cancer, categorized by the levels of salivary nitrate and nitrite and NRase activity, showed a higher cancer risk associated with nitrite > 7.5 μg/ml (OR: 3.0, C.I.: 1.0–9.3), nitrite > 40 μg/ml (OR: 4.3, C.I.: 1.4–13.3) and NRase activity > 50 nmol/ml/min (OR: 2.9, C.I.: 1.1–7.4). Our findings suggest that increased consumption of dietary nitrate and nitrite is associated with elevated levels of salivary nitrite. Together with the increased activity of salivary NRase, these observations may explain, at least in part, the role of nitrate and nitrite in the development of oral cancer in individuals from an area with a high burden of N-nitroso precursors.
Highlights
High levels of dietary nitrate have long been considered risk factors in the development of various types of cancer in humans [12]
Increased nitrate and nitrite burden is linked to higher incidences of several types of malignancies in human populations such as upper aerodigestive tract [24], oral [13,19], stomach [14], and bladder cancers [1,2]
In the present study we measured the levels of nitrate and nitrite and the activity of nitrate reductase (NRase) in the saliva of oral cancer patients and normal individuals in order to evaluate the involvement of these factors in the etiology of oral cancer
Summary
High levels of dietary nitrate have long been considered risk factors in the development of various types of cancer in humans [12]. Nitrate can be reduced to nitrite in the oral cavity and react with amines and amides to form Nnitroso compounds (NOC) [4]. Nitrate is highly concentrated in humans by the salivary glands and secreted into the saliva at levels that may reach 10-fold higher than plasma concentrations [28]. Saliva contains little or no nitrite when secreted, but nitrate is rapidly reduced to nitrite after exposure to the oral cavity. This reduction occurs mainly on the posterior surface of the tongue [9] in a reaction catalyzed by the nitrate reductase (NRase) enzyme. NRase is present in mammalian cells and can be synthesized in many anaerobic, mouth colonizing, nitratereducing micro-organisms when exposed to low oxygen tension [9]
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