O-6-Alkylguanines, Dietary N-Nitroso Compounds, And Their Precursors In Gastric Cancer

Several N-nitroso compounds, present in foods and beverages or formed in the stomach from their precursors, act as alkylating agents. By using a highly reliable technique (high-resolution gas chromatography-mass spectrometry with negative-ion chemical ionization and selected ion recording), we measured a series of specific W-alkylguanines in snap-frozen paired stomach tissue samples (tumor and noninvolved mucosa) obtained at surgery from 24 gastric cancer patients identified in Florence, Italy. Samples of noninvolved mucosa had higher levels of total O-6-alkylguanines and more frequently detectable levels (54%) than tumor samples (29.2%). O-6-propylguanine and O-6-methylguanine were the single adducts most frequently detected in noninvolved mucosa and tumor tissue, respectively. Tumor samples showed higher levels of total O-6-alkylguanines in female patients (p = 0.03) and among those with a diffuse histological type (p = 0.06) or seronegative for Helicobacter pylori CagA antibodies (p = 0.06). Mean dietary nitrate intake was significantly higher inpatients with detectable levels of adducts in tumor samples (p = 0.03). Estimated intakes of dimethylamine and N-nitrosodimethylamine correlated with total levels of O-6-alkylguanines in noninvolved gastric mucosa. These findings, although based on a small series of cases, support a role for N-nitroso compounds from dietary sources in the etiology of gastric cancer.