Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: findings from the Shanghai Cohort Study

Abstract

N-nitroso compounds (NOCs) formed during food processing and the in vivo nitrosation of secondary amines or amides in the presence of nitrites are believed to play a significant role in the development of gastric cancer. Epidemiological data examining the associations between biomarkers of exposure to NOCs and the risk of developing gastric cancer are sparse. A nested case-control study was conducted within the Shanghai Cohort Study, a prospective cohort of 18,244 middle-aged and older men. Urinary levels of N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), nitrate and nitrite as well as serum H. pylori antibodies were quantified in samples from 191 incident gastric cancer cases and 569 individually matched control subjects. Odds ratios and 95% confidence intervals for gastric cancer associated with elevated levels of urinary NOCs were calculated from logistic regression models for all subjects as well as for subgroups stratified by H. pylori status. Urinary NMTCA level was significantly higher in alcohol drinkers than nondrinkers. Compared with all control subjects, cancer patients overall had comparable levels of urinary nitrate, nitrite, and NOCs. Among individuals with negative H. pylori antibodies, elevated urinary nitrate level was associated with increased risk of gastric cancer. The multivariate-adjusted ORs (95%) for gastric cancer in the second and third tertiles of nitrate were 3.39 (0.82~13.96) and 4.18 (0.96~18.13), respectively, compared with the lowest tertile of nitrate (P for trend = 0.057). The present study did not support a direct relationship between urinary biomarkers of N-nitroso-compounds and their precursors and the risk of developing gastric cancer in a high-risk population.