Dietary nitrosamines, heterocyclic amines, and risk of gastric cancer: a case-control study in Uruguay. Weisburger JH, Raineri R. Dietary factors and the etiology of gastric cancer. Bingham SA, Pignatelli B, Pollock JR, et al. The FFQ used in NL was very similar to the one used in ON, but it was based on a validated instrument that had been adapted for the Canadian population(27; 28; 29); and for the present study, it was modified slightly to include foods indigenous to the Newfoundland population (e.g., salted/pickled meat and smoked/pickled fish). Nutrient intake and risk of subtypes of esophageal and gastric cancer. cured meats. NDMA, N-nitrosodimethylamine; ENOC, endogenous N-nitroso compound exposure index. HHS Vulnerability Disclosure, Help A gastric cancer case-control study that considered H. pyloriinfection status observed interactions between plasma vitamin C concentrations and ENOC (8). Sci Rep. 2021 Jan 13;11(1):1181. doi: 10.1038/s41598-020-80859-0. We also tested for potential interactions between plasma vitamin C concentrations and the 3 exposures of interest. N-Nitroso compounds are known to be potent animal carcinogens. There were some extreme outliers for NDMA, ENOC, and nitrite. Results of studies in human subjects with this test led to the following conclusions: (1) The process of endogenous nitrosation in humans is influenced by many factors; therefore, determination only of nitrate and nitrite in body fluids is insufficient to assess the extent of nitrosation in man in vivo. and transmitted securely. van Loon AJ, Botterweck AA, Goldbohm RA, Brants HA, van Klaveren JD, van den Brandt PA. Cross AJ, Leitzmann MF, Gail MH, Hollenbeck AR, Schatzkin A, Sinha R. Buiatti E, Palli D, Decarli A, et al. 1999 Jul 15;443(1-2):129-38. doi: 10.1016/s1383-5742(99)00015-0. The https:// ensures that you are connecting to the Lin K, Yu SJ, Zhang JJ, et al. All the covariates were entered into the model as categorical variables. For the endogenous NOC exposure, an index (the ENOC) was previously determined (8) by using the estimated iron content from meat intake and fecal ATNC formation from several human controlled-diet studies (912). In the present analysis, we excluded individuals who reported a history of familial adenomatous polyposis and those who provided insufficient information on diet and related risk factors(23). [15][16] A yeast study has shown that N-nitrosamines can perturb amino acid metabolism and mitochondrial function.[17]. However, evidence of their effect on human cancers is inconclusive, and further investigations are needed. Another study carried out by de Roos et al. Self-administered food frequency questionnaires were collected from 957 pathologically confirmed pancreatic ductal adenocarcinoma cases and 938 frequency-matched controls. Results: There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend 0.05). Subsequent studies showed that approximately 90% of the 300 nitrosamines tested were carcinogenic in a wide variety of animals. Would you like email updates of new search results? Mutat Res. Introduction Synthetic/inorganic fertilizers are widely used in agriculture as low-cost and rapid source of plant nutrients that result in an enormous rise in plants productivity. Bookshelf Furthermore, in this study, only rectal cancer, but not colon cancer, was significantly associated with NDMA exposure. This extensive database was compiled by conducting a literature search (19802003) to identify sources of data on the concentrations of nitrosamines in foods. Thus, endogenous formation of NOC can occur at various sites in the body. These findings further demonstrate the potential joint effects of NDMA with vitamin E and NDMA with protein. Yun Zhu was awarded by the Newfoundland and Labrador Centre for Applied Health Research through a Master's fellowship. FOIA The .gov means its official. Protein has been suggested to be the main source of secondary and tertiary amines (32; 33), the indispensable agents for the nitrosation reaction. 2022 Feb 8;152(2):439-447. doi: 10.1093/jn/nxab372. Percentages may not sum to 100% because of rounding. 2021 Dec;74(6):3161-3173. doi: 10.1002/hep.32046. However, these studies did not account for the potential effect modification by Helicobacter pylori, which is an important risk factor for gastric cancer. Vitamin C may protect against carcinogenesis by inhibiting the nitrosation process and, thus, reducing endogenous nitrosation formation (13). Dietary exposures to NDMA, nitrite and nitrate were calculated for the NL population using the instrument developed by Howe et al(30). Individuals with missing values were excluded from specific analyses. Welch AA, Luben R, Khaw KT, Bingham SA. Overall, human exposure to NOCs and subsequent cancer risk has not been studied extensively. Finally, the family history questionnaire was used to assess family history of cancer. Plasma vitamin C is a more accurate biomarker than is dietary vitamin C, which has dietary measurement-error issues. The number of food items assessed in these studies ranged from 28 to 474 items (32). Nitrosamine intake and gastric cancer risk. This site needs JavaScript to work properly. Nitrate, nitrite, dimethylnitrosamine and N-nitrosopyrrolidine in some Chinese food products. The positive association between NDMA exposure and cancer risk was observed in men but not in women. Dietary intakes of both NDMA and ENOC were significantly higher in cases than in noncases. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. A possible reason for the observed heterogeneity is that the NOC-carrying faeces that are of a higher concentration when reaching the mucosa of the rectum than the colon would lead to a stronger relationship with rectal cancer (8). The specific alkylating agents vary with the nitrosamine, but all are proposed to feature alkyldiazonium centers. Dietary NDMA (g NDMA/d, presented in ng), ENOC (g/d), and dietary nitrite (mg nitrite/d) data were obtained from the EPIC-EURGAST study (8). Table 5 summarises the OR of CRC for NDMA-containing food items. All calculations were carried out with the SAS software (version 9.2). We initially hypothesised that there may be a positive association between nitrate/nitrite intakes and CRC risk, as they are precursors of NDMA, but this was not confirmed when cancers in different subsites were analyzed together. Sun Z, Wang PP, Roebothan B, et al. For continuous analyses, we log transformed the values. N-Nitroso compounds are known to be potent animal carcinogens. A potential mechanism underlying this association might be the formation of alkylating agents, resulting in DNA modification(4; 21). The initial model was adjusted only for age, sex and province of residence. However, vitamins C and E may exert an inhibitory effect in cancer carcinogenesis by blocking the nitrosation process by quenching free radicals in their anaerobic reaction with nitrite(34), thus reducing the endogenous synthesis of NOC (8; 11). Careers. A mathematical model to create indices of nitrate, nitrite, and N-nitrosamine exposures, both exogenous and endogenous, is described in this paper. Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H. J Epidemiol. Bethesda, MD 20894, Web Policies National Library of Medicine Cox proportional regression adjusted for age and sex. Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer. Foods. Those who did not respond were sent a reminder card, and a follow-up call was made if needed. Design: This was a prospective study of 23,363 men and women, aged 4079 y, who were recruited in 19931997 and followed up to 2008. When we combined colon and rectal cancer cases (n = 413) in our study, the relative risk estimate was >1.0 but not significant. Thus, many studies investigating the relationship between NOC and cancers (8) do consider nitrates and nitrites. When we included information on the intakes of vitamins C and E from supplements, similar patterns were observed; yet none of the interaction terms of total vitamins (diet plus supplement) with NDMA was statistically significant (data not shown). Berends JE, van den Berg LMM, Guggeis MA, Henckens NFT, Hossein IJ, de Joode MEJR, Zamani H, van Pelt KAAJ, Beelen NA, Kuhnle GG, de Kok TMCM, Van Breda SGJ. Although pickled vegetables may contain NDMA, they are also rich in vitamin E, which may neutralise the deleterious effect of NDMA or, alternatively, vegetables may also contain other anti-carcinogens that reduce the cancer risk(21). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). Coffee consumption and future risk of type 2 diabetes among women with a history of gestational diabetes, Physical activity and individual plasma phospholipid SFAs in pregnancy: a longitudinal study in a multiracial/multiethnic cohort in the United States, Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes a prospective study, About The American Journal of Clinical Nutrition, Receive exclusive offers and updates from Oxford Academic, A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC), Associations of dairy product consumption with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC)Italy cohort. Nitrate, nitrite, and nitrosable amino-compounds in food and drugs, chemistry of N-nitroso-compounds]. Sirirungreung A, Hansen J, He D, Huang X, Ritz B, Heck JE. Yet Hua Loh and others, N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)Norfolk Study, The American Journal of Clinical Nutrition, Volume 93, Issue 5, May 2011, Pages 10531061, https://doi.org/10.3945/ajcn.111.012377. From the NFCCR, we identified 1159 pathologically confirmed incident CRC cases on the basis of International Classification of Disease (ICD)-9 codes: (153.0-153.9, 154.0-154.3 and 154.8) or ICD-10 codes: (18.0-18.9, 19.9 and 20.9). 1997 Aug;6(4):351-6. doi: 10.1097/00008469-199708000-00006. Zheng J, Daniel CR, Hatia RI, Stuff J, Abdelhakeem AA, Rashid A, Chun YS, Jalal PK, Kaseb AO, Li D, Hassan MM. A single multiplicative interaction term was used to assess the potential interactive effects between NDMA, nitrite, and ENOC and plasma vitamin C concentrations on cancer risk, and its significance was tested by using the likelihood ratio test. EPIDEMIOLOGIC STUDIES OF DRINKING . Only minimal studies have specifically reported results in relation to CRC and showed a positive association with NOC intake(6; 8). (37) has shown nitrate exposure from drinking-water to be associated with increased colon cancer risk among individuals with low vitamin C intakes (>10 years with average nitrate intake>5 mg/l and vitamin C intake <131.8mg/d v. nitrate intake 5 mg/l and vitamin C intake 131.8mg/d: OR 2.0, 95%CI 1.2, 3.3). However, the wide range of possible NOCs that can be formed and the rapid metabolism of NOCs in the body pose challenges to these methods (25). However, the evidence from findings has not been consistent and conclusive. Statistical analyses were performed with STATA statistical software (version 10.1; StataCorp, College Station, TX). NOCs can be formed endogenously from dietary precursors like nitrate, nitrite and amines. Schriftenr Ver Wasser Boden Lufthyg. Knekt P, Jarvinen R, Dich J, Hakulinen T. Rowland IR, Granli T, Bockman OC, Key PE, Massey RC. Grosse Y, Baan R, Straif K, Secretan B, El GF, Cogliano V. Jakszyn P, Bingham S, Pera G, et al. Statistical significance was considered at p<0.05. This study had both strengths and limitations. The lack of an association between nitrate/nitrite intakes and CRC risk is in line with the results of previous prospective studies(6; 8). For a large number of N-nitroso compounds a comparison of their carcinogenic effects in rats and Syrian golden hamsters has been made. European Prospective Investigation into Cancer and Nutrition, Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment, Nutritional methods in the European Prospective Investigation of Cancer in Norfolk, Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers, The CAFE computer program for nutritional analysis of the EPIC-Norfolk food frequency questionnaire and identification of extreme nutrient values, Development of a food database of nitrosamines, heterocyclic amines, and polycyclic aromatic hydrocarbons, Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study, Metabolism of acyclic and cyclic N-nitrosamines by cultured human colon, Endogenous N-nitrosation in man assessed by measurement of apparent total N-nitroso compounds in faeces, Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence, Intake of nitrate and nitrite and the risk of gastric cancer: a prospective cohort study, A prospective study of red and processed meat intake in relation to cancer risk, Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies, A case-control study of gastric cancer and diet in Italy: II. Following adjustment for confounders, we observed significant positive associations for NDEA (ORQ4 versus Q1 = 2.28, 95% CI = 1.71-3.04, Ptrend < 0.0001) and NDMA from plant sources (ORQ4 versus Q1 = 1.93, 95% CI = 1.42-2.61, Ptrend < 0.0001) with pancreatic cancer. Online prediction tools for melanoma survival: A comparison. La Vecchia C, D'Avanzo B, Airoldi L, et al. There was evidence that plasma vitamin C concentrations had an effect-modifier role between cancer risk and NDMA exposure. We investigated cancers associated with the gastrointestinal tract and also common cancers in this study population. For this study, data for dietary NDMA, ENOC, and dietary nitrite were only available for the validated FFQ method (20). The demonstrated efficacy of certain vitamins as nitrosation inhibitors also provides a plausible interpretation of epidemiological findings that have shown protective effects of fruits and vegetables (sources of vitamins and polyphenols) against various malignancies and particularly stomach cancer. eCollection 2023 Mar. 1998 Apr;56(4 Pt 1):95-105. doi: 10.1111/j.1753-4887.1998.tb01721.x. 1. HRs of cancer risk at specific cancer sites are shown in Table 5. After adjustment, no statistically significant associations were observed between consumption of beer or pickled vegetables examined in the present study and CRC risk. Dietary N-nitrosodimethylamine (NDMA), endogenous N-nitroso compound exposure index (ENOC), and dietary nitrite exposure in relation to cancer risk1. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Tannenbaum SR, Wishnok JS, Leaf CD. The authors are grateful to the NFCCR and OFCCR staff for their help with data collection. CRC risk became more pronounced (OR 3.05; 95%CI 1.43,6.51) than would be expected if NDMA exposure was high and vitamin E intake was low (P for interaction=0.017). Maternal dietary exposure to N-nitroso compounds (NOC) or to their precursors during pregnancy has been associated with risk of childhood brain tumors.Cured meat is one source of exposure to dietary NOC and their precursors. Modifiable and Non-Modifiable Risk Factors for the Development of Non-Hereditary Pancreatic Cancer. However, the test for interaction was not statistically significant (P for interaction=0.46). Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of the epidemiologic evidence. For female participants, there were additional questions relating to reproductive factors. As an outgrowth, the present study further examined the associations between other foods with potentially high contents of nitrosamines and CRC risk in this population and consequently found a dose-dependent increase with the increased consumption of meats rich in NDMA; however, pickled vegetables were observed to non-significantly elevate the risk of developing CRC. Environ Health Perspect. Loh YH, Jakszyn P, Luben RN, et al. 8600 Rockville Pike Objective: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)Norfolk, United Kingdom, study. Therefore, more efforts are needed to develop a comprehensive and high-quality food composition database of NOC for humans, which would allow more precise identification of dietary NOC values. The essential feature of Nnitroso compounds is the N-N=O structure; the R 1 and R 2 groups attached to the amine . Nitrate and nitrite as precursors of the NOCs (e.g., NDMA) are suspected of playing a key role in cancer carcinogenesis through the induction of DNA-damaging metabolites, like aldehydes and. Colorectal cancer (CRC) is one of the most serious types of colorectal health problems in North America, but its incidence rates vary geographically(1; 2). However, subjects who consumed NDMA-containing meat at the highest tertile were 1.47 times as likely to have been diagnosed with CRC as individuals who consumed NDMA-containing meats at the lowest tertile, although the overall trend was not significant. Schriftenr Ver Wasser Boden Lufthyg. Attempts have been made to obtain direct estimations of endogenous NOCs via urine- and fecal-output chemical analyses. Although bacterial strains possessing enzymes that catalyse N-nitrosamine formation at neutrality have been isolated from the gastric juice of achlorhydric subjects, their precise role in gastric carcinogenesis remains to be clarified. Knekt P, Jarvinen R, Dich J, et al. A case-control study of gastric cancer and diet in Italy: II. N-nitroso compounds (NOCs) include two chemical classes, nitrosamines and nitrosamides, which are formed by the reaction of amines and amides, respectively, with nitrosating agents derived from nitrite (1-4).Nitrosamides, which are direct alkylating agents that do not require metabolic activation (2, 5), are potent neuro-carcinogens in animal models, especially through . A Cox proportional hazards regression model was used to examine the relation between cancer incidence and dietary intake of NDMA, ENOC, and dietary nitrite. Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Medicina (Kaunas). The .gov means its official. As a result, a total of 896 subjects in ON and 281 subjects in NL were excluded, resulting in a final sample size of 1760 cases and 2481 controls for this pooled analysis. A 2006 systematic review supports a "positive association between nitrite and nitrosamine intake and . Using a validated and comprehensive N-nitroso database developed to estimate total NOCs and important individual NOCs from food intake, we investigated dietary exposure to NOCs in relation to pancreatic cancer in a large matched case-control study. Because this was a prospective study, a dietary assessment was conducted before the diagnosis of cancer, which minimized the recall bias and reverse causation. Processed foods and metabolism of heme iron are potential sources of N-nitroso compounds. Carcinogenic activity and other adverse effects of N-nitroso compounds might be prevented by consuming vitamin C and antioxidants containing fruits and vegetables. Hazard ratio; 95% CI in parentheses (all such values). Written informed consent was obtained from all the participants at recruitment. Mendelian randomization: how it can--and cannot--help confirm causal relations between nutrition and cancer. Z. was awarded a Master's fellowship by the Newfoundland and Labrador Centre for Applied Health Research. 23 Red meat consumption was associated with the alkylating signature in colorectal . N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study. Here the authors investigate the role of dietary sources of N-nitroso compounds (NOCs) in bladder cancer risk, taking into account both ingestion of preformed NOCs as well as the often overlooked role of endogenous NOC formation. Nitrate, nitrite and N-nitroso compounds in foods. The present study was supported by the Canadian Institutes Of Health Research Team Grant (CIHR-CPT79845), the Canadian Institutes of Health Research Team in Interdisciplinary Research on Colorectal Cancer Studentship (205835) and the National Cancer Institute, National Institutes of Health under RFA #- CA-08-502, and by cooperative agreements with members of the Colon Cancer Family Registry and principal investigators: Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). Pobel D, Riboli E, Cornee J, et al. Results of studies in human subjects with this test led to the following conclusions: (1) The process of endogenous nitrosation in humans is influenced by many factors; therefore, determination only of nitrate and nitrite in body fluids is insufficient to assess the extent of nitrosation in man in vivo. Background: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. The EPIC-Norfolk study is a prospective cohort of 25,639 men and women, aged 4079 y, who were recruited between 1993 and 1997 in Norfolk, United Kingdom. We also evaluated the potential effect modification of dietary nitrate by dietary vitamin C. A borderline significant interaction between dietary nitrate and vitamin C was observed (P for interaction= 0.04), with a greater risk being observed among those with high nitrate and low vitamin C intakes (data not shown). Language links are at the top of the page across from the title. There was an overall increased cancer risk with NDMA when cancers of the gastrointestinal tract were analyzed as combined. The organic chemistry of nitrosamines is well developed with regard to their syntheses, their structures, and their reactions. Perhaps the exposure level in women was not high enough to reach the biological level that could exert carcinogenic effects. De Stefani E, Boffetta P, Mendilaharsu M, et al. An average of all available suitable values was assigned when several matches for a food item were available. Moreover, NDMA has been shown to induce DNA adduct formation in human colonocytes (23, 24). Scanlan RA, Barbour JF. In humans, there is supporting evidence for a role of NOCs in the cause of certain cancers such as gastric, esophageal, nasopharyngeal, and colon cancers (2, 3). Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. Published by Oxford University Press. An official website of the United States government. Human beings are exposed to preformed NOCs from sources such as tobacco products, diet, drugs, and occupational environments and NOCs produced in vivo (3). Clipboard, Search History, and several other advanced features are temporarily unavailable. N-nitroso compounds (NOCs) can induce cancer in about 40 different animal species, including higher primates, and are carcinogenic in multiple organs in animals (1). As a library, NLM provides access to scientific literature. Epub 2013 Jun 14. There was evidence of effect modification between dietary vitamin E and NDMA. Bookshelf For Permissions, please email: journals.permissions@oup.com. Careers. sharing sensitive information, make sure youre on a federal Background: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. There were significant interactive effects between plasma vitamin C concentrations and dietary NDMA intake on cancer risk in simple age- and sex-adjusted and multivariate models. Adjusted OR and 95% CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. Descriptive statistics, including means and percentages, were used to show the distribution of baseline characteristics in cases and noncases. Mayne ST, Risch HA, Dubrow R, et al. (ABSTRACT TRUNCATED AT 400 WORDS), MeSH Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study. This synthesis method is relevant to the generation of nitrosamines under some biological conditions. Endogenously, NOCs that comprise nitrosamines and nitrosamides can be generated when nitrite reacts with the degradation products of amino acids in the stomach. Corresponding Author: Peizhong Peter Wang, MD, PhD, Division of Community Health & Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, A1B 3V6, Phone: (709)-777-8571, Fax: (709)-777-7382, The publisher's final edited version of this article is available at, Canadian Cancer Statistics 2012, Canadian Cancer Society, Statistics Canada. Cotterchio M, Boucher BA, Manno M, et al. official website and that any information you provide is encrypted We analyzed the compositional and metabolic profile of the bacteriome in. This method estimated the ENOC on the basis of the iron content from meat intakes, and it has previously been shown that the correlation between iron and ENOC was very high (8). In the case of formation of carcinogenic nitrosamines in the stomach from dietary nitrite (used as a processed meat preservative), ascorbic acid markedly decreases nitrosamine formation in the absence of fat in the meal, through inhibition. Accessibility The site is secure. Nonfasting blood samples were collected in plain and citrate bottles. (8) found an increased risk of gastrointestinal cancers (hazard ratio:1.13; 95%CI 1.00,1.28), specifically of rectal cancer (hazard ratio 1.46; 95%CI 1.16,1.84), with per 1 SD (0.05 g) increase of dietary NDMA intake in Norfolk, UK, although no significant associations were observed between dietary nitrite intake and cancer risk. 1992 Dec;2(6):272-7. doi: 10.1097/00008571-199212000-00005. Exposure to nitrosatable drugs during pregnancy and childhood cancer: A matched case-control study in Denmark, 1996-2016. This site needs JavaScript to work properly. N-nitroso compound formation is inhibited by dietary antioxidants found in vegetables and fruits / 12-14 /, which may partly account for the . Careers, Unable to load your collection due to an error. Hazard ratios were measured with corresponding 95% CIs. They feature a nitroso group (NO +) bonded to a deprotonated amine.Most nitrosamines are carcinogenic in nonhuman animals. CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR: 1.47; 95% CI: 1.03,2.10; p-trend=0.20). In the case of ENOC, an increased HR was only observed in men in age-adjusted analyses but not in multivariate analyses. [5][6] They usually are produced by the reaction of nitrous acid (HNO2) and secondary amines. Dietary N-Nitroso Compounds and Risk of Hepatocellular Carcinoma: A USA-Based Study. On the basis of the digestive system route, the esophagus, stomach, colon, and rectum were logically the sites that were susceptible to exogenous NOCs. Kalus WH, Filby WG. 2022 Jul 22;58(8):978. doi: 10.3390/medicina58080978. In July 2021, FDA announced it would not object to certain manufacturers distributing varenicline tablets containing N-nitroso-varenicline above FDA's acceptable intake limit, but below the. Please enable it to take advantage of the complete set of features! However, similar to the EURGAST study (8), this endogenous index was far greater than the estimated dietary NOC exposure as measured by NDMA intake (0.06 g NDMA/d) in this study. The O level indicates the completion of schooling to the age of 15 y, and the A level to indicates the completion of schooling to the age of 17 y. HHS Vulnerability Disclosure, Help In all instances, greater exposure to endogenous NOC was found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers of disease state: ascorbic acid efficiently lowered the body burden of intragastrically formed NOC. Dietary N-nitrosodimethylamine (NDMA), endogenous N-nitroso compound exposure index (ENOC), and dietary nitrite exposure in relation to site-specific cancer risk1. Although some of our findings probably reflect reverse causation bias due to lower meat intake in cases with latent disease, biologically plausible findings for pancreatic carcinogens, NDEA and NDMA, warrant further prospective investigation. An official website of the United States government. In ON, approximated intakes of NOC were determined based on the report of the United States Department of Agriculture. The positive association with NDMA was present only in subjects with low plasma vitamin C concentrations. A detailed description of the storage method has been previously described (16). government site. Most nitrosamines are carcinogenic in nonhuman animals. These were formally compared by using the t test for continuous variables and the chi-square test for categorical variables. First, case-control studies of dietary factors in relation to cancers are mostly subject to recall and selection biases(39). The nitrous acid usually arises from protonation of a nitrite. The semiquantitative EPIC-FFQ was designed to establish the average consumption of foods during the preceding year (21). Similar findings were observed for ENOC but only in the age- and sex-adjusted model (P for interaction = 0.009) (data not shown). Calibration of the dietary questionnaire for the Canadian Study of Diet, Lifestyle and Health cohort. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). All the foods were divided into tertiles and entered as categorical variables into the model that included potential confounders. Statistical hypotheses of trend were tested based on the median of each category of intake. In this large prospective study of dietary NOCs in relation to cancer risk, we showed that gastrointestinal cancer incidence was associated with dietary NDMA but not with ENOC and nitrite. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Meat processing such as curing (e.g. (3) Formation of endogenous NOC was assessed by the NPRO test in: (i) subjects living in high- and low-incidence areas for stomach cancer in northern Japan, Costa Rica and Poland; (ii) subjects with different habits of betel-quid chewing and tobacco use; (iii) patients with urinary bladder infections; and (iv) subjects infested with liver fluke in Thailand. Risk patterns by histologic type. Endogenous formation of nitrosamines and oxidative DNA-damaging agents in tobacco users. We further examined risk of cancer for dietary NDMA stratified by plasma vitamin C concentrations. by adding nitrates or nitrites) or smoking can lead to the formation of potentially cancer-causing (carcinogenic) chemicals such as N-nitroso-compounds (NOC) and polycyclic aromatic hydrocarbons (PAH). This present study has both strengths and limitations. Food Cosmet Toxicol. Two categories, rectal cancer and other cancers showed increased risks with significant HRs of 1.46 and 1.11 (for an increment of 0.05 g NDMA), respectively. Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk. Cox proportional regression adjusted for age, sex, BMI, cigarette smoking status, alcohol intake, energy intake, physical activity status, educational level, menopausal status (in women), and plasma vitamin C concentrations. National Library of Medicine We acknowledge the limitation of the small number of cases for esophageal and stomach cancers in our study. The estimated mean intake of NDMA in our study was relatively low compared with that in other studies (0.080.55 g NDMA/d) (32). There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001). Howe GR, Harrison L, Jain M. A short diet history for assessing dietary exposure to N-nitrosamines in epidemiologic studies. When case groups with various tumor subsites were compared independently with controls, differences in the association between NDMA intake and CRC risk emerged (table 3). In recent years, several N-nitroso compounds (NOC) have been detected in pickled/processed meats, including volatile N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine, which have been shown to be carcinogenic in a variety of laboratory animals(4; 5); yet, evidence of the carcinogenicity of NOC in humans is lacking. There were data available for analyses on 23,363 participants (10,783 men and 12,580 women) with a mean age at recruitment of 58.6 y. Rogers MA, Vaughan TL, Davis S, et al. Values are hazard ratios (HRs); 95% CIs in parentheses. 8600 Rockville Pike One prospective . Unauthorized use of these marks is strictly prohibited. These 3 exposures were analyzed as continuous variables (per approximate 1-SD increase) and as categorical variables (quartiles). Pickled meat consumption and colorectal cancer (CRC): a case-control study in Newfoundland and Labrador, Canada. In this study, we examined the relation between dietary NOCs (measured by NDMA), endogenous NOCs (ENOC), and dietary nitrite, and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)Norfolk study. To avoid having a disproportionate effect of extreme outliers when these were used as continuous variables, outliers of NDMA (4.4% of the study population), ENOC (0.7% of the study population), and nitrite (0.1% of the study population) were recoded as a maximum of the mean 4 SD of each exposure. Supported by the Medical Research Council and Cancer Research UK, the Red Temtica de Investigacin Cooperativa en Cncer (RETICC; DR06/0020-0015; to PJ) of the Spanish Ministry of Health, and the Singapore Health Services (YHL). A significant NDMA-CRC association was observed in NL than in ON. Bartsch H, Ohshima H, Shuker DE, Pignatelli B, Calmels S. Mutat Res. In the selection method of the multivariate model, all the potential confounders based on the literature and previous studies were entered in a stepwise fashion. [11], Nitrite and nitrosamine intake are associated with risk of gastric cancer and oesophageal cancer.[12]. The relatively long duration from the point of reference could also adversely affect recall. Similar patterns have been reported in other investigations (20; 32; 35; 36). Although both differential and non-differential reporting of dietary exposures may result in biased risk estimates, non-differential misclassification is expected to bias the results toward the null. Although risk estimates observed in men and women were in the same direction, only risk estimates for men were significant in all analyses. 1.. IntroductionThe N-nitroso compounds include many multipotent carcinogens that are capable, as a group, of inducing a great variety of tumors, depending on the chemical structure of the compound and the species to which it is administered 1, 2.Since they are complete carcinogens, N-nitroso compounds must be able to act as both initiators and promotors in the two-stage mechanism described by . Afterwards, the correlation between iron intake from meat and fecal ATNC levels was assessed, and the ENOC was predicted by using the linear regression accordingly (8). The synergistic effect between NDMA and protein could explain the significant positive association. Several NOCs are potential human carcinogens, including N -nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent. Zhao J, Halfyard B, Roebothan B, et al. MeSH Before There were significant interactive effects between plasma vitamin C concentrations and dietary NDMA intake on cancer risk in age- and sex-adjusted and multivariate models. Silvester KR, Bingham SA, Pollock JR, Cummings JH, ONeill IK. Effect of plasma vitamin C concentrations and dietary N-nitrosodimethylamine exposure (per SD) on cancer risk1. In organic chemistry, nitrosamines (or more formally N-nitrosamines) are organic compounds with the chemical structure .mw-parser-output .template-chem2-su{display:inline-block;font-size:80%;line-height:1;vertical-align:-0.35em}.mw-parser-output .template-chem2-su>span{display:block;text-align:left}.mw-parser-output sub.template-chem2-sub{font-size:80%;vertical-align:-0.35em}.mw-parser-output sup.template-chem2-sup{font-size:80%;vertical-align:0.65em}R2NN=O, where R is usually an alkyl group. Similar to our study, the EURGAST study reported that ENOC was positively but not significantly associated with gastric cancer risk (8). sharing sensitive information, make sure youre on a federal doi: 10.2903/j.efsa.2023.7884. Percentages may not sum to 100% because of rounding. The site is secure. The patterns that we observed suggest that vitamins E may modify the effect of NDMA on CRC risk. Hosmer DW, Hosmer T, Le Cessie S, et al. Nitrosating agents and NOC can also be synthesized endogenously in reactions mediated by bacteria and activated macrophages. Introduction. An estimated 4575% of the total NOC exposure is contributed by endogenous synthesis (7). Using a validated and comprehensive N-nitroso database developed to estimate total NOCs and important individual NOCs from food intake, we investigated dietary exposure to NOCs in relation to pancreatic cancer in a large matched case-control study. Association between Dietary Nitrate, Nitrite Intake, and Site-Specific Cancer Risk: A Systematic Review and Meta-Analysis.

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