Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite andN-nitroso compounds: a follow-up study

Knekt, Paul; Järvinen, Ritva; Dich, Jan; Hakulinen, Timo

doi:10.1002/(sici)1097-0215(19990315)80:6<852::aid-ijc9>3.0.co;2-s

Cited by 240 publications

(80 citation statements)

References 18 publications

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“…In line with the findings from another prospective study (Kearney et al, 1996), a nonsignificant positive association was suggested between intake of vitamin D and rectal cancer risk. In the present study population, fish consumption contributed greatly to the intake of dietary vitamin D. In our previous study, we reported an increased colorectal cancer risk with high consumption of salted and smoked fish (Knekt et al, 1999).…”

Section: Discussionmentioning

confidence: 56%

Prospective study on milk products, calcium and cancers of the colon and rectum

et al. 2001

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Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14 -1.46, P for trend 0.09) for milk and 0.37 (95% CI ¼ 0.12 -1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI ¼ 0.08 -1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI ¼ 1.00 -4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation.

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Section: Discussionmentioning

confidence: 56%

Prospective study on milk products, calcium and cancers of the colon and rectum

et al. 2001

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“…One of the proposed mechanisms for the cancer-promoting effects of red meat is DNA damage due to the conversion of nitrates and nitrites in processed meat into NOCs, multi-site carcinogens that can proceed to form covalent adducts with DNA bases and potentially contribute to a wide range of malignancies (Mirvish, 1995; Bingham et al, 1996; Knekt et al, 1999; Parnaud et al, 2000; Santarelli et al, 2008; Kim et al, 2013; Dellavalle et al, 2014; Catsburg et al, 2014). In vitro exposure of human colorectal cells to NOCs can indeed induce DNA alkylation (Povey et al, 2002) and consequent mutation in genes involved in DNA damage control and in cell proliferation and differentiation such as K- RAS (Hebels et al, 2009; Hebels et al, 2010).…”

Section: Existing Theories To Explain Increased Disease Risks Of Rmentioning

confidence: 99%

“…While studies have shown a positive dose response in the levels of apparent total NOCs in the fecal samples of human volunteers given different quantities of red meat (Hughes et al, 2001; Bingham et al, 2002), many epidemiological studies found modest or no association between dietary NOCs and several types of cancer, including esophagus (Keszei et al, 2013; González et al, 2006), stomach (Keszei et al, 2013; Song et al, 2015), colorectal (Knekt et al, 1999; Dellavalle et al, 2014), and bladder cancer (Catsburg et al, 2014; Ferrucci et al, 2010; Zeegers et al, 2006). Of course, the absence of a biomarker for NOC long-term exposure as well as methods for distinguishing endogenous nitrosation from dietary intake of nitrate/nitrite limit our ability to validate the proposed association of NOC exposure with the risk of colorectal cancer.…”

Section: Existing Theories To Explain Increased Disease Risks Of Rmentioning

confidence: 99%

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

Alisson-Silva

Kawanishi

Varki

2016

Molecular Aspects of Medicine

131

103

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One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine–N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat. Even the frequently mentioned polycyclic aromatic carcinogens arising from high temperature cooking methods are not red meat specific, as these are also generated by grilling poultry or fish, as well as by other forms of cooking. The traditional explanations that appear to be more red meat specific invoke the impact of N-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation. However, heme can be denatured by cooking, high levels of plasma hemopexin will block its tissue delivery, and much higher amounts of heme likely originate from red blood cell breakdown in vivo. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects. Also, none of these mechanisms explain the apparent human propensity i.e., other carnivores have not been reported at high risk for all these diseases. A more recently proposed hypothesis involves infectious agents in beef from specific dairy cattle as agents of colorectal cancer. We have also described another mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into the tissues of red meat consumers and the subsequent interaction with inflammation-provoking antibodies against this “xenoautoantigen”. Overall, we conclude that while multiple mechanisms are likely operative, many proposed theories to date are not specific for red meat, and that the viral and xenoautoantigen theories deserve further consideration. Importantly, there are potential non-toxic dietary antidotes, if the xenoautoantigen is indeed correct.

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“…Evidence of an etiological association between exposure to N-nitroso compounds and gastric cancer has been difficult to obtain (13). However, many different epidemiological studies (ecological, casecontrol, and cohort) have reported an increased risk of aerodigestive tract cancer associated with frequent consumption of foods with a high nitrosamine content, such as salted, smoked, and pickled foods (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

O⁶-Alkylguanines, Dietary N-Nitroso Compounds, and Their Precursors in Gastric Cancer

Palli¹,

Saieva²,

Coppi³

et al. 2001

Nutrition and Cancer

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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 O6-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 O6-alkylguanines and more frequently detectable levels (54%) than tumor samples (29.2%). O6-propylguanine and O6-methylguanine were the single adducts most frequently detected in noninvolved mucosa and tumor tissue, respectively. Tumor samples showed higher levels of total O6-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 in patients with detectable levels of adducts in tumor samples (p = 0.03). Estimated intakes of dimethylamine and N-nitrosodimethylamine correlated with total levels of O6-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.

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Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite andN-nitroso compounds: a follow-up study

Cited by 240 publications

References 18 publications

Prospective study on milk products, calcium and cancers of the colon and rectum

Prospective study on milk products, calcium and cancers of the colon and rectum

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

O⁶-Alkylguanines, Dietary N-Nitroso Compounds, and Their Precursors in Gastric Cancer

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Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite andN-nitroso compounds: a follow-up study

Cited by 240 publications

References 18 publications

Prospective study on milk products, calcium and cancers of the colon and rectum

Prospective study on milk products, calcium and cancers of the colon and rectum

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

O6-Alkylguanines, Dietary N-Nitroso Compounds, and Their Precursors in Gastric Cancer

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Product

Resources

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O⁶-Alkylguanines, Dietary N-Nitroso Compounds, and Their Precursors in Gastric Cancer