Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered

The Effect of N-nitrosodimethylamine (NDMA) on Bax and Mcl-1 Expression in Human Neutrophils

In the present study we examined a role of pro-apoptotic Bax and anti-apoptotic Mcl-1 proteins, participating in the regulation of intrinsic apoptosis pathway in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA), the environmental xenobiotic. For the purpose comparison, the same studies were conducted in autologous peripheral blood mononuclear cells (PBMCs). The production of cytochrome c by PMNs was also determined. A deficit of anti-apoptotic Mcl-1 and overexpression of the pro-apoptotic protein Bax suggest that the apoptosis process in human neutrophils exposed to NDMA is dependent on changes in the expression of these proteins. PMNs were more sensitive to NDMA than PBMCs

Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites

INTRODUCTION: Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and oncogene activation. Potential links exist between environmental agents and DNA methylation, but the destabilizing effects of environmental exposures on the DNA methylation machinery are not understood within the context of breast cancer aetiology. METHODS: We assessed genome-wide changes in methylation patterns using a unique methylation profiling technique called amplification of intermethylated sites (AIMS). This method generates easily readable fingerprints that represent the investigated cell line's methylation profile, based on the differential cleavage of DNA with methylation-specific isoschisomeric restriction endonucleases. RESULTS: We validated this approach by demonstrating both unique and reoccurring sites of genomic hypomethylation in four breast carcinoma cell lines treated with the cytosine analogue 5-azacytidine. Comparison of treated with control samples revealed individual bands that exhibited methylation changes, and these bands were excized and cloned, and the precise genomic location individually identified. In most cases, these regions of hypomethylation coincided with susceptible target regions previously associated with chromosome breakage, rearrangement and gene amplification. Similarly, we observed that acute benzopyrene exposure is associated with altered methylation patterns in these cell lines. CONCLUSION: These results reinforce the link between environmental exposures, DNA methylation and breast cancer, and support a role for AIMS as a rapid, affordable screening method to identify environmentally induced DNA methylation changes that occur in tumourigenesis

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: Findings from the Shanghai cohort study

Background: N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods: A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results: Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion: The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection

Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Multiple <it>N</it>-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to <it>N</it>-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of <it>N</it>-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds.</p> <p>Methods</p> <p>Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics.</p> <p>Results</p> <p>Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 μg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity.</p> <p>Conclusions</p> <p>Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and <it>N</it>-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.</p

Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution

DNA Damage and Reactive Nitrogen Species are Barriers to Vibrio cholerae Colonization of the Infant Mouse Intestine

Ingested Vibrio cholerae pass through the stomach and colonize the small intestines of its host. Here, we show that V. cholerae requires at least two types of DNA repair systems to efficiently compete for colonization of the infant mouse intestine. These results show that V. cholerae experiences increased DNA damage in the murine gastrointestinal tract. Agreeing with this, we show that passage through the murine gut increases the mutation frequency of V. cholerae compared to liquid culture passage. Our genetic analysis identifies known and novel defense enzymes required for detoxifying reactive nitrogen species (but not reactive oxygen species) that are also required for V. cholerae to efficiently colonize the infant mouse intestine, pointing to reactive nitrogen species as the potential cause of DNA damage. We demonstrate that potential reactive nitrogen species deleterious for V. cholerae are not generated by host inducible nitric oxide synthase (iNOS) activity and instead may be derived from acidified nitrite in the stomach. Agreeing with this hypothesis, we show that strains deficient in DNA repair or reactive nitrogen species defense that are defective in intestinal colonization have decreased growth or increased mutation frequency in acidified nitrite containing media. Moreover, we demonstrate that neutralizing stomach acid rescues the colonization defect of the DNA repair and reactive nitrogen species defense defective mutants suggesting a common defense pathway for these mutants

Development of estimates of dietary nitrates, nitrites, and nitrosamines for use with the short willet food frequency questionnaire

<p>Abstract</p> <p>Background</p> <p>Studies have suggested that nitrates, nitrites, and nitrosamines have an etiologic role in adverse pregnancy outcomes and chronic diseases such as cancer. Although an extensive body of literature exists on estimates of these compounds in foods, the extant data varies in quality, quantified estimates, and relevance.</p> <p>Methods</p> <p>We developed estimates of nitrates, nitrites, and nitrosamines for food items listed in the Short Willet Food Frequency Questionnaire (WFFQ) as adapted for use in the National Birth Defects Prevention Study. Multiple reference databases were searched for published literature reflecting nitrate, nitrite, and nitrosamine values in foods. Relevant published literature was reviewed; only publications reporting results for items listed on the WFFQ were selected for inclusion. The references selected were prioritized according to relevance to the U.S. population.</p> <p>Results</p> <p>Based on our estimates, vegetable products contain the highest levels of nitrate, contributing as much as 189 mg/serving. Meat and bean products contain the highest levels of nitrites with values up to 1.84 mg/serving. Alcohol, meat and dairy products contain the highest values of nitrosamines with a maximum value of 0.531 μg/serving. The estimates of dietary nitrates, nitrites, and nitrosamines generated in this study are based on the published values currently available.</p> <p>Conclusion</p> <p>To our knowledge, these are the only estimates specifically designed for use with the adapted WFFQ and generated to represent food items available to the U.S. population. The estimates provided may be useful in other research studies, specifically in those exploring the relation between exposure to these compounds in foods and adverse health outcomes.</p