Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

School for Oncology and Developmental Biology, Department of Epidemiology, Maastricht University, Maastricht, Netherlands.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 11/2012; 97(1). DOI: 10.3945/ajcn.112.043885
Source: PubMed


BACKGROUND: Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. OBJECTIVE: We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. DESIGN: A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. RESULTS: Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. CONCLUSION: These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

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    • "The classical VNA (NDMA, NPYR, NPIP, NDEA) accounted for >90% of the exposure to VNAs. The exposure levels estimated in the present work for the VNA are in the same order of magnitude as the exposure levels reported by others (Table 1)(Keszei et al., 2013;Tricker et al., 1991). The exposure levels estimated for the NVNA though seems to be lower than the intake suggested by Tricker and Preussmann (1991). "
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    ABSTRACT: Recent epidemiological studies show a positive association between cancer incidence and high intake of processed meat. N-nitrosamines (NA) in these products have been suggested as one potential causative factor. Most volatile NA (VNA) are classified as probable human carcinogens, whereas the carcinogenicity for the majority of the non-volatile NA (NVNA) remains to be elucidated. Danish adults (15-75 years) and children (4-6 years) consume 20 g and 16 g of processed meat per day (95th percentile), respectively. The consumption is primarily accounted for by sausages, salami, pork flank (spiced and boiled) and ham. This consumption results in an exposure to NVNA of 33 and 90 ng kg bw-1 day-1 for adults and children, respectively. The exposure to VNA is significantly lower amounting to 0.34 and 1.1 ng kg bw-1 day-1 for adults and children, respectively. Based on a BMDL10 of 29 µg kg bw-1 day-1 a MOE value ≥17000 was derived for the exposure to NA known to be carcinogenic (VNA including NSAR), indicating an exposure of low concern. The exposure to the NVNA is substantially higher and if found of toxicological significance the exposure may be of concern. Copyright © 2015. Published by Elsevier Ltd.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2015; 80. DOI:10.1016/j.fct.2015.03.008 · 2.90 Impact Factor
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    • "Therefore, the increased incidence of BC in Shantou, and in China too, was likely due to endogenous cultural factors (cooking with lard) plus externally-introduced risk factors (passive cigarette smoke exposure, sedate life style). However, we did not confirm the consumption of pickled food, cured fish and fish sauce as risk factors (Inoue-Choi et al., 2012; Lin et al., 2009; Keszei et al., 2013). Perhaps, these are not consistent risk factors across different populations. "
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    International Journal of Hygiene and Environmental Health 01/2015; 218(3). DOI:10.1016/j.ijheh.2015.01.001 · 3.83 Impact Factor
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    • "An updated review in 2012 (Bryan et al., 2012) came to the firm conclusion that there is no association, in humans, between nitrosamine formation and gastric cancer. The Netherlands Cohort Study (Keszei et al., 2013), in which 120,000 men and women were tracked for 16.3 years, concluded that, although nitrosamines in the diet may cause oesophageal carcinomas , there was no clear association with other gastric subtypes. Although a diet of processed meat (including the wartime delicacy of Spam) may be unattractive to the discriminating palate, it does not constitute a cancer hazard. "
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    ABSTRACT: The presence of nitrite in the human diet was thought to be a hazard as that could result in the formation of secondary nitrosamines, known to cause gastric cancers in animal models. Nitrite is added to food as an antibacterial agent and can also be formed by the action of reductase enzymes, present in the mouth, on nitrate. However, the epidemiological evidence linking gastric cancers in humans with nitrite and nitrate in the diet is lacking. In addition, recent work has shown that nitrate in the diet has potential benefit as it can cause a fall in blood pressure. The early use of nitrate in traditional Chinese medicine for the treatment of angina is described.
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