Case-control study on influence of methionine, nitrite, and salt on gastric carcinogenesis in northern Italy

A new mutagen, 2-chloro-4-methylthiobutanoic acid, has recently been identified from a nitrite-treated Japanese salted fish. Its structure suggests that it derives from methionine in the presence of salt and nitrite. We thus considered the interaction between intake of methionine, salt, and nitrites on gastric cancer risk using data from a case-control study conducted in Northern Italy on 746 cases of incident histologically confirmed gastric cancer and 2,053 controls in hospital for acute nonneoplastic nondigestive tract disorders. Compared with subjects reporting low-methionine and low-salt intake, the odds ratios (ORs) were 2.4 [95% confidence interval (CI) = 1.5 - 4.0] for those reporting low-salt and high-methionine, 1.5 (95% CI = 1.0 - 2.2) for those with high-salt and low-methionine, and 2.8 (95% CI = 1.9 - 4.2) for those with high-salt and high-methionine intake. Likewise, with reference to nitrites, compared with subjects with low-methionine and low-nitrite intake, the ORs were 1.9 (95% CI = 1.3 - 2.6) in the high-methionine and low-nitrite stratum, 1.5 (95% CI = 1.0 - 2.1) in the low-methionine and high-nitrite stratum, and 2.5 (95% CI = 1.9 - 3.2) in the high-methionine and high-nitrite stratum. All these estimates were statistically significant. Thus the present findings from a large case-control study conducted in a relatively high-incidence area for gastric cancer suggest that a diet rich in methionine, salt, and nitrite is associated with increased gastric cancer risk.