Article

Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference

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  • National Cancer institute
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Abstract

Meats cooked at high temperatures (frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well-done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. We conducted a population-based case-control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n = 176) and esophagus (n = 143) between July 1988 and June 1993 and 502 controls. The dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. High intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. after excluding those who reported usually barbecuing/grilling, a source of both PAHc and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. Int. J. Cancer, 71:14–19, 1997. © 1997 Wiley-Liss. Inc.

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... This implies an average consumption frequency of grilled, broiled and pan-fried meats of 1.4 times per week, i.e. 73 HAA-containing meals per year. In comparison , WARD et al. [34] reported a much higher frequency of four times per week for just steaks, roasts and hamburgers. Another noteworthy aspect of the estimation methodology is the HAA content database used in calculations. ...
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Purpose Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. Methods Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). Results Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25–2.03), always using table salt (aOR 1.33, 95% CI 1.16–1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01–1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82–1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. Conclusion Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.
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Background: The role of allium vegetables on gastric cancer (GC) risk remains unclear. Methods: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. Results: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. Conclusions: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.
Article
The relationship between red and processed meat and its risk towards colorectal carcinoma (CRC) is not fully explored in literature. Polycyclic aromatic hydrocarbons (PAHs) are pro-carcinogenic molecules that are ingested with meat cooked at high temperatures. The metabolic conversion of PAHs to carcinogenic diol epoxides is in part mediated by the aryl hydrocarbon receptor (AhR)-dependent induction of CYP1A1. This study aims to examine and expression profiles and polymorphisms of the AHR (aryl hydrocarbon receptor) gene which is involved in the metabolic conversion of PAHs in patients with CRC. Genetic analysis was done in matched cancer and non-neoplastic tissues from 79 patients diagnosed with CRCs. Low AHR mRNA expression was associated mucinous colorectal adenocarcinoma. Exon 10 of AHR showed that 27% of patients had the rs2066853 single nucleotide polymorphism resulting in an arginine to lysine change at codon 554. This variant was significantly associated with a lower likelihood of perineural invasion, presence of synchronous cancer, and multiple colorectal polyps. Furthermore, rs2066853 individuals were significantly more likely to be of more advanced age and have a more favourable tumour grade and pathological stage. These results imply the pathogenic roles of AHR in PAH-associated colorectal carcinogenesis.
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One of the most notable changes in the epidemiology of esophageal cancer (EC) is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet, and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations, and EAC risk; published in English; without a time filter. The Newcastle-Ottawa Scale was used to assess risk of bias. The results are stratified by risk factor. A total of 106 publications were included. Half of the case-control studies were judged as high quality, whilst practically all cohort studies were judged as high quality. Body mass index and waist circumference were associated with increased EAC risk. Physical activity did not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a Western diet. Alcohol does not seem to be related to EAC, whereas smokers, particularly heavy smokers, have an increased risk of EAC. Prevention remains the best option to avert EAC. Comprehensible and easy to follow recommendations should be provided to all subjects. Protocol ID number: CRD-42021228762, no funds received.
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At this point in time, the evidence of a link between well-done meat intake and the incidence of cancer is stronger than it was 20 years ago. Several cohort and case-control studies have confirmed this evidence, and have shown a higher odd ratio and increased exposure to heterocyclic amines (HCAs) among those who frequently consume red meat. However, in most epidemiological studies, dietary assessment, combined with analytical data, is used to estimate the intake of HCAs, which has many inconsistencies. In addition, there is a lack of findings indicating a substantial correlation between various factors, like types of raw meat, types of meat products, and cooking methods that directly or indirectly influence the occurrence of cancer. Although numerous mitigation strategies have been developed to reduce HCAs levels in meat, there is still a high prevalence of carcinogenesis caused by HCAs in humans. The aim of this review is to summarise conflicting reports, address shortcomings and identify emerging trends of cutting-edge research related to HCAs.
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Adinandra nitida leaf extract (ANE) is rich in phenols and flavonoids. In this study, the effects of ANE as an additive on the formation of major heterocyclic amines (HCAs), namely, PhIP, norharman and harman, in both chemical model systems and fried chicken patties were explored. In model systems, treatment with various amounts of ANE (0, 15, 30, 45, 60 mg) led to the most effective inhibition of PhIP, norharman and harman, with levels reduced by 47.88%, 49.73% and 29.63% when treated with 45 mg, 60 mg and 60 mg, respectively. Further, the effect of diverse dosages of ANE (0, 0.2, 0.4, 0.6%, w/w) on the formation of HCAs in chicken patties fried at 170 °C and 190 °C was evaluated. Statistics showed that the temperature significantly increased the formation of HCAs. Total HCA contents of patties fried at 170 °C and 190 °C ranged from 1.52 ng g⁻¹ to 2.52 ng g⁻¹ and from 6.05 ng g⁻¹ to 13.76 ng g⁻¹, respectively. The inhibitory efficacy of various concentrations of ANE on the total HCA content was higher (38.95–56.03%) in patties fried at 190 °C than at 170 °C (18.65–40.08%). External parts of the meat patties showed higher HCA contents than the interior. The current study presents evidence that ANE at moderate dosages can reduce the formation of HCAs in fried chicken. By extension it suggests that ANE has potential applications as a natural antioxidant for preventing the formation of HCAs in foods.
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The Gulf of Milazzo (north-eastern Sicily) has been recognized as Italian Site of National Interest (SNI; areas characterized by high level of contamination with potential effects on human health) in 2005 because of its high level of pollution. In this study we measured the concentration of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polyBrominated diphenyl ether (PBDE) in seawater and sediments sampled from the Gulf of Milazzo in order to assess (i) the environmental status of contamination, and (ii) cancer and non-cancer human health risk potentially due to dermal absorption from contaminated seawater and/or ingestion of contaminated fish. Particularly, POPs content in pelagic and demersal fish of different size classes (small, medium, and large) were estimated, starting from the measured seawater and sediments concentrations, using the KABAM model. In particular, Monte Carlo simulation techniques were applied to address uncertainty in assessment of the risk and to provide quantitative estimates of probability of exposition. Ingestion of contaminated pelagic and demersal fish was the dominant pathway of exposition with high probability of significant cancer risk (Ingestion Cancer Risk >10–4) and significant non-cancer risk (Hazard Index >1). No human health risks emerged to be associated to dermal adsorption from contaminated seawater. Benzo(a)pyrene show the highest Ingestion Cancer Risk with respect to the other PAHs, while the highest Hazard Index for non-cancerogenic molecules was estimated for the PBDE47 congener.
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: Whether the risk of gastric cancer varies by the types of meat consumption still remains disputable. The purpose of this meta-analysis was to identify the exact associations that red, processed, and white meat have with gastric cancer. We searched relevant studies in Medline, EMBASE, and the Cochrane Library before November 2018, including cohort and case-control studies. We used random-effect models to estimate the adjusted relative risk (RR), and Egger’s tests to evaluate publication bias. Through stepwise screening, 43 studies were included in this analysis (11 cohort studies and 32 case-control studies with 16,572 cases). In a meta-analysis for the highest versus lowest categories of meat consumption, both red (RR: 1.41, 95% confidence interval (CI): 1.21–1.66) and processed (RR: 1.57, 95% CI: 1.37–1.81) meat consumption were positively associated with gastric cancer risk, while white meat consumption was negatively associated with gastric cancer risk (RR: 0.80, 95% CI: 0.69–0.92). In a dose–response meta-analysis, the RRs of gastric cancer were 1.26 (95% CI: 1.11–1.42) for every 100 g/day increment in red meat consumption, 1.72 (95% CI: 1.36–2.18) for every 50 g/day increment in processed meat consumption, and 0.86 (95% CI: 0.64–1.15) for every 100 g/day increment in white meat consumption. The increase of white meat consumption may reduce the risk of gastric cancer, while red or processed meat may increase the risk of gastric cancer. Further studies are required to identify these associations, especially between white meat and gastric cancer.
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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is an abundant dietary carcinogen, formed during high-temperature cooking of meat. In this study, we investigated whether clinically relevant ATP-binding cassette (ABC) efflux transporters can modulate PhIP-induced colorectal carcinogenesis in vivo using wild-type (WT), Bcrp1−/−; Mrp2−/−; Mrp3−/− and Bcrp1−/−; Mdr1a/b−/−; Mrp2−/− mice. We used a physiological mouse model of colorectal cancer; a combination of a single high-dose oral PhIP administration (200 mg/kg), followed by administering a colonic inflammatory agent, dextran sodium sulfate (DSS), in drinking water for 7 days. Pilot experiments showed that both knockout strains were more sensitive to DSS-induced colitis compared to WT mice. Lack of these transporters in mice also led to clearly altered disposition of activated PhIP metabolites after a high-dose oral PhIP administration. The results suggest that Mdr1a/1b, Bcrp1 and Mrp2 contributed to biliary excretion and Mrp3 to sinusoidal secretion of the pre-carcinogenic metabolite N2-OH-PhIP. The levels of a genotoxicity marker, PhIP-5-sulphate, were at least 4- and 17-fold reduced in the intestinal tissue and intestinal content of both knockout strains compared to WT mice. In line with these findings, the level of colon carcinogenesis was reduced by two- to four-fold in both knockout strains compared to WT mice when PhIP and DSS treatments were combined. Thus, perhaps counterintuitively, reduced activity of these ABC transporters may in part protect from PhIP-induced colon carcinogenesis. Collectively, these data suggest that ABC transporters are important in protecting the body from inflammatory agents such as DSS, in the disposition of carcinogenic metabolites, and in determining the sensitivity to dietary PhIP-induced carcinogenesis.
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Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children that can be affected by maternal diet. The aim of this study was to evaluate maternal dietary risk factors of ALL. We searched MEDLINE, Cochrane Library, Springer Link, Wiley Online, Science Direct, Mosby, ISI Web of Science, OVID, ProQuest, and Scopus from database inception until February 2, 2016. Two reviewers scanned titles, abstracts, and keywords of articles after excluding duplicates. We included case-control studies evaluating the relationship between maternal diet during pregnancy and childhood ALL. The search resulted in 2,940 papers, of which 11 full-text articles met the criteria for inclusion in the review and were analyzed. The finding of these studies suggest that maternal diet composed largely of vegetables, fruits, and protein sources before and during pregnancy can reduce the risk of ALL in offspring. Maternal alcohol intake had no effect. Nevertheless, inherent limitations of case-control studies like measurement error, random error, recall bias, and selection bias preclude conclusive evidence. Persuading pregnant women to follow a healthy diet rich in fruits, vegetables, and protein may reduce the risk of childhood ALL. Avoiding alcohol intake seems prudent.
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The relationships between dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett’s esophagus (BE) risk remain inconclusive. We conducted a systematic review and meta-analysis to summarize the available evidence on these issues. PubMed, EMBASE and the Cochrane Library were searched for studies published from inception through October 2015. A total of eight studies were included in this analysis. Fruit intake was not associated with BE risk (OR = 0.65, 95% CI = 0.37–1.13), but vegetable intake was strongly associated with BE risk (OR = 0.45, 95% CI = 0.29–0.71). Saturated fat, red meat and processed meat intakes were not associated with BE risk with OR = 1.25 (95% CI = 0.82–1.91), OR = 0.85 (95% CI = 0.61–1.17) and OR = 1.03 (95% CI = 0.73–1.46), respectively. Dietary vegetable not fruits intake may be associated with decreased BE risk. Fat and red and processed meat intakes may not contribute to an increased BE risk. Well-designed, large prospective studies with better established dose-response relationships are needed to further validate these issues.
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Eating out of the home has been positively associated with body weight, obesity, and poor diet quality. While cooking at home has declined steadily over the last several decades, the benefits of home cooking have gained attention in recent years and many healthy cooking projects have emerged around the United States. The purpose of this study was to develop an evidence-based conceptual framework of healthy cooking behavior in relation to chronic disease prevention. A systematic review of the literature was undertaken using broad search terms. Studies analyzing the impact of cooking behaviors across a range of disciplines were included. Experts in the field reviewed the resulting constructs in a small focus group. The model was developed from the extant literature on the subject with 59 studies informing 5 individual constructs (frequency, techniques and methods, minimal usage, flavoring, and ingredient additions/replacements), further defined by a series of individual behaviors. Face validity of these constructs was supported by the focus group. A validated conceptual model is a significant step toward better understanding the relationship between cooking, disease and disease prevention and may serve as a base for future assessment tools and curricula.
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In the present study, the effect of various natural food condiments (garlic, ginger, pepper, tomato and onion) on the formation of heterocyclic amines (HAs) in cooked camel meat was studied. In control sample, the amount of HAs MeIQx, 4,8‐DiMeIQx and PhIP were obtained between 2.10 and 5.22 ng/g, while, MeIQ and IQ were found less than quantification limit. The camel meat cooked with different food condiments, the HAs were found in lesser amounts. MeIQx, 4,8‐DiMeIQx and PhIP were detected from 0.42 to 2.83 ng/g, however, MeIQ and IQ were not indentified in any analyzed samples. Consequently, camel meat cooked by various food condiments illustrates the capability to reduce the HAs formation. Such information may be elucidated because of the presence of antioxidants in such condiments which might have pro‐oxidative effects with the subsequent formation of peroxyl radicals or by the scavenging of oxygen or free radicals. Practical Applications This is the first study relating to the inhibition of HAs by means of some common food condiments in cooked camel meat. In this work, five HAs such as MeIQx, 4,8‐DiMeIQx, PhIP, MeIQ and IQ have been studied in camel meat samples thermally processed with or without food condiments. Our results evidently demonstrate that the formation of HAs in cooked camel meat is highly affected by using food condiments. The current study also illustrates that the concentrations of HAs can be kept at low levels by cooking the meat that include food condiments. The obtained results could be used to estimate the human intake of HAs either in Saudi Arabia or global and supplied to the search of good food condiments that reduce the threat of exposure to HAs, and thus to advance the food security and quality.
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Barrett esophagus is described as a condition in which the normal squamous epithelium of the distal esophagus is replaced by abnormal columnar mucosa containing intestinal metaplasia. The prevalence of gastroesophageal reflux is 20% and Barrett esophagus is 0.4% in Turkey. Cronic mucosa irritation related to gastroesophageal reflux is the most important cause of the development of Barrett esophagus. In addition, obesity and some other diseases may result in Barrett esophagus development. Barrett esophagus is the only known precursor to esophageal adenocarcinoma and to date, it is one of the cancer types that has the most rapidly increasing incidence. Carcinogenic risk is 30 times higher than that in the normal population. Treatment should have the purpose of controlling symptoms of gastroesophageal reflux, preventing acid and duodenal reflux into esophagus, preventing the development of complications, such as erosion, peptic ulcus, stricture, preventing proximally extension of intestinal metaplasia, inducing regression of intestinal metaplasia to the normal mucosa, preventing the development of dysplasia. inducing regression of dysplasia to nondysplastic cells, and preventing the development of adenocarcinoma. The grade of the dysplasia determines the treatment modality. Whereas in patients with non-dysplastic or low grade dysplasia, follow-up, medical treatment, antireflux surgery or ablation therapy may be appropriate, esophagectomy should be preferred in patients with high grade dysplasia.
Article
Background: Gastric cancer is a major health issue in China. The risk factors are related to the environment and nutrition, including salt intake. Salt taste sensitivity is the capacity to identify the flavor of salt and the salt taste sensitivity threshold (STST) can influence salt appetite. Methods: A 1: 2 matched hospital based case-control study including 300 cases with newly histological confirmed diagnosis of gastric cancer and 600 controls that were cancer and gastric disease free was performed. A self-designed questionnaire was used to collect information on possible risk factors of gastric cancer, and a salt taste sensitivity test was used to measure the STST for all subjects. Conditional logistic regression was employed to calculated odds ratios (ORs) and 95% confidence intervals (95% CI). Results: Salted and preserved meat (adjusted OR=2.12 (1.71-3.67) for <= 3 times/week; adjusted OR=3.12(2.13-4.76) for >= 4 times/week), pickled vegetables (3.13 (1.74-5.33) for >= 4 times/week) and salted fish intake (adjusted OR=1.46 (1.05-1.97 for >= 4 times/week) demonstrated significant associations with gastric cancer. There is a significant positive association between high STST and gastric cancer, and the adjusted OR was 2.05 (1.68-2.5), and the STST score was positively associated with the frequency of salted and preserved meat. When we used STST >= 5 as a cut point, people with STST >= 5 were at 5.71 (3.18-6.72) times greater risk of gastric cancer than those with STST >= 5. Also, the cut point of STST >= 5 had a best sensitivity and specificity for predicting gastric cancer risk detection (sensitivity of 73.7%, specificity of 57.0%). Conclusion: Salt and salted food intake are etiological factors for gastric cancer, and a high STST is strongly associated with gastric cancer risk.
Chapter
Noncommunicable chronic diseases such as inflammatory bowel diseases, cancer, diabetes, obesity, and pulmonary, cardiovascular, and neurodegenerative diseases are becoming the leading cause of death throughout the world. Unhealthy diet, smoking, lack of exercise, stress, radiation exposure, and environmental pollution are among the common causes of chronic diseases. Most of these risk factors are closely linked to chronic inflammation, which leads to the development of various chronic diseases. Diets high in fruits, vegetables, legumes, fiber, and certain spices have been shown to suppress chronic inflammation and prevent the development of chronic diseases. In this review we discuss the evidence for the molecular basis of inflammation and how inflammation mediates most chronic diseases. We also present clinical and experimental models showing the molecular effects of selected spices and spice-derived nutraceuticals such as cardamonin, curcumin, capsaicin, gingerol, thymoquinone, and piperine on these inflammatory pathways and the potential role of nutraceuticals in preventing chronic diseases.
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The association between meat consumption and cancer risk has been studied extensively by a range of approaches, from highly controlled animal studies to large prospective epidemiologic studies. Many studies have reported an increased risk for colorectal cancer for those with a diet high in red or processed meat. Less definitive evidence suggests that high meat consumption may also increase the risk of a variety of other cancers, including some of the more prevalent cancers, such as breast and prostate cancers, as well as less common cancers, such as pancreatic, esophageal, and kidney cancers. There are several proposed mechanisms to support an association between meat and cancer, including preservation and processing procedures that can increase exposure to N-nitroso compounds. In addition, high-temperature cooking methods increase the formation of heterocyclic amines and polycyclic aromatic hydrocarbons, both of which are mutagenic. This article discusses the observational data and then elaborates on the mechanistic data relating meat intake to carcinogenesis.
Article
This study used a quick interview and calculation for a preliminary estimation of dietary exposure to heterocyclic aromatic amines (HAA) MeIQx (2-amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine), as well as acrylamide (AA) in 94 adult women from eastern Croatia. Subjects were administered a questionnaire to obtain information on their anthropometric and socio-economic characteristics, and on their dietary habits. Intake of main sources of HAA and AA was determined and combined with literature data on their food levels. Both high and low estimates were calculated by the use of maximum and minimum published levels. The low estimate approach produced mean daily exposures to MeIQx (0.93 ± 0.77 ng∙kg-1 body weight, bw) and PhIP (2.34 ± 2.49 ng∙kg-1 bw), as well as a provisional total HAA intake of 4.43 ng∙kg-1 bw per day, that fit better within the range of results reported by other authors. Similarly, the low estimate of AA daily exposure (122.66 ± 60.00 ng∙kg-1 bw) was below the lower end of the range determined by the European Food Safety Authority but more plausible considering other published levels. © 2014 Národné polnohospodárske a potravinárske centrum (Slovakia).
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Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people, however the etiology of these cancers is poorly understood. We therefore investigated associations of body- mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux, and use of non-steroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients, and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux, and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR=8.06, 95%CI: 4.52, 14.37; Peffect modification =0.01) and BMI (ORBMI ≥30 vs. <25 =4.19, 95%CI: 2.23, 7.87; Peffect modification =0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers. This article is protected by copyright. All rights reserved. © 2015 UICC.
Article
Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population-based case-control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20–69) newly diagnosed in 1988–1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1–2.1) and 1.9 (95% CI 1.3–2.9) in the highest quartile of intake among men (p for trend = 0.02) and women (p = 0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p = 0.07) and women (p = 0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non-cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved. Int. J. Cancer 76:659–664, 1998. Published 1998 Wiley-Liss, Inc.†
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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is produced during cooking and is mutagenic to bacteria and cultured mammalian cells, was found to induce high incidences of colon and mammary carcinomas in F344 rats when administered at a concentration of 400 p.p.m. in the diet for 52 weeks. Since PhIP is the most abundant of the mutagenic heterocyclic amines in cooked meat and fish, the compound might be related to malignancies of the colon and breast in humans.
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In epidemiologic studies, individuals may be misclassified with respect to exposure to a risk factor for disease. Such misclassification causes the relative risk of disease associated with the exposure in the population to be biased toward the null value. Here, a formula is derived for the apparent relative risk under misclassification (R) as a function of the sensitivity (U) and specificity (V) of the test for exposure and of the true relative risk (R) and true prevalence of exposure (P(E] in the population. The relative influence of U and V on the bias in R depends both on R and on P(E), with U tending to be more influential at higher values of P(E). When there is misclassification of exposure, variation in P(E) may bias comparisons of relative risk between groups or exposures, either by producing spurious differences or by masking true differences, and may generate spurious trends associated with a third variable such as age. Because the possible effects of misclassification of exposure on relative risk are complex and not easily generalized, the potential degree of bias should be evaluated individually in each situation.
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Heterocyclic aromatic amines (HAAs) are mutagenic and carcinogenic compounds found in meats cooked at high temperatures. Although chicken is consumed in large quantities in the United States, there is little information on its HAA content. The objective of this study was to measure the five predominant HAAs (IQ, MeIQ, MeIQx, DiMeIQx, and PhIP) in chicken cooked by various methods to different degrees of doneness. Chicken breasts were panfried, oven-broiled, or grilled/barbecued. Whole chickens were roasted or stewed. Skinless, boneless chicken breasts were cooked to three degrees of doneness: just until done, well done, or very well done. High levels of PhIP (ranging from 12 to 480 ng/g cooked meat) were found in chicken breasts when panfried, oven-broiled, and grilled/barbecued but not in while roasted or stewed chicken. PhIP concentration increased in skinless, boneless chicken breast with longer cooking time, higher internal temperature, and greater degree of surface browning. PhIP concentration was also high in chicken breasts cooked with skin and bones. MeIQx and DiMeIQx levels increased with the degree of doneness, whereas IQ and MeIQ were not detectable in any of these chicken samples. Certain cooking methods produce PhIP, a known colon and breast carcinogen in rodents and possibly a human carcinogen, at substantially higher levels in chicken than has been reported previously in red meat.
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To study the role of hot mate drinking, alcohol, tobacco, and diet in esophageal cancer, a case-control study including 131 cases and 262 hospital controls was carried out in La Plata, Argentina. In multivariate analyses, statistically significant increases in risk were detected for alcohol, tobacco, and some dietary factors but not for hot mate drinking. A strong dose-response relationship was observed with the amount of alcohol consumed daily but not with the number of cigarettes smoked. The odds ratio for those drinking more than 200 ml of ethanol/day compared to nondrinkers was 5.7 (95% confidence interval, 2.2-15.2). An increased risk was also observed for those eating barbecued meat more than once a week (odds ratio, 2.4; 95% confidence interval, 1.2-4.8) as compared to those eating it less than once a week, and a reduction in risk was associated with daily consumption of nonbarbecued beef as compared to those eating it less than daily. Concerning mate drinking, the only variable that showed an effect was the temperature at which mate is drunk. Those who reported drinking mate hot or very hot as compared to those drinking it warm had an increase in risk (odds ratio, 1.7; 95% confidence interval, 1.0-2.9). Our findings strengthen the evidence for an important role of alcohol and tobacco in esophageal carcinogenesis but do not provide strong support for a role of hot mate drinking.
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The metabolic activation of food-borne heterocyclic amines to colon carcinogens in humans is hypothesized to occur via N-oxidation followed by O-acetylation to form the N-acetoxy arylamine that binds to DNA to give carcinogen-DNA adducts. These steps are catalyzed by hepatic cytochrome P4501A2 (CYP1A2) and acetyltransferase-2 (NAT-2), respectively, which are known to be polymorphic in humans. On the basis of this proposed metabolic activation pathway, patients at greatest risk to develop colorectal cancer or nonfamilial polyps should be those who possess both the rapid NAT-2 and rapid CYP1A2 phenotypes and are exposed to high dietary levels of carcinogenic heterocyclic amines. Using a method that involves caffeine administration and high pressure liquid chromatographic analysis of urinary metabolites, we have determined the CYP1A2 and NAT-2 phenotypes of 205 controls and 75 cancer/polyp cases. Exposure information was obtained using a dietary and health habits questionnaire. Both the rapid CYP1A2 and rapid NAT2 phenotypes were each slightly more prevalent in cases versus controls (57% and 52% versus 41% and 45%, respectively). However, the combined rapid CYP1A2-rapid NAT-2 phenotype was found in 35% of cases and only 16% of the controls, giving an odds ratio of 2.79 (P = 0.002). Univariate analysis of the questionnaire indicated that age, rapid-rapid phenotype, and consumption of well done red meat were associated with increased risk of colorectal neoplasia. Furthermore, a logistic regression model that included age (as a continuous variable), consumption of well done red meat, and rapid-rapid phenotype as independent covariates gave odds ratios of 1.08, 2.08, and 2.91, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Meats cooked at high temperatures contain HCAs which are known animal carcinogens. Epidemiologie studies of colon cancer using crude surrogates for HCAs exposure (eg., doneness) have produced suggestive findings that these compounds may be human carcinogens as well. In order to improve exposure assessment of HCAs we have developed a database of HCAs concentrations in commonly consumed meat items cooked by various techniques and degrees of doneness We have found that HCAs levels and types were dependent on multiple factors, including type of meat, cooking technique, place of preparation (e.g. home, restaurant, or "fast-food" restaurant), as well as the degree of doneness and surface browning/charring We have used these data to develop a questionnaire which is being used in multiple case-control and cohort studies. In addition, we have carried out a metabolic study among 66 subjects who consumed low and high levels of HCAs to evaluate potential biomarkers of HCA exposure and to explore potential sources of inter-individual variability in the activation (eg., cytochrome P4501A2) and detoxification of these compounds. These studies will help to clarify the role of HCAs in human carcinogenesis.
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This chapter reviews the literature on surrogate sources of dietary information. The availability of dietary information from surrogates, the validity of such information, and the implications of using surrogates on study design and data analysis are considered.
Article
Consider two matched independent series of binomial variates whose odds ratios are assumed constant, i.e. ψ = (p1iq2i)/(p2iq1i)(i =1, ..., b). Under the assumption that all marginals in each of the 2 × 2 tables are fixed, exact and approximate methods of point and interval estimation of ψ are reviewed and derived. The methods are illustrated and compared in a numerical example.
Article
Consider a random sample, x1, …, xn, from a Poisson distribution. The Rao-Blackwell theorem and the completeness property of this distribution are exploited to show that E(kj\σxi = X) = x¯ (i = 1, 2, …) and to find higher conditional moments of the sample cumulants. Some possible applications to the testing of the fit of the Poisson distribution are suggested.
Article
A case-control study was conducted in high- and low-risk areas of Italy to evaluate reasons for the striking geographic variation in gastric cancer (GC) mortality within the country. Personal interviews with 1,016 histologically confirmed GC cases and 1,159 population controls of similar age and sex revealed that the patients were more often of lower social class and resident in rural areas and more frequently reported a familial history of gastric (but not other) cancer. After adjusting for these effects, case-control differences were found for several dietary variables, assessed by asking about the usual frequency of consumption of 146 food items and beverages. A significant trend of increasing GC risk was found with increasing consumption of traditional soups, meat, salted/ dried fish and a combination of cold cuts and seasoned cheeses. The habit of adding salt and the preference for salty foods were associated with elevated GC risk, while more frequently storing foods in the refrigerator, the availability of a freezer and use of frozen foods lowered risk. Reduced GC risk were associated with increasing intake of raw vegetables, fresh fruit and citrus fruits. Lowered risk was also related to consumption of spices, olive oil and garlic. Neither cigarette smoking nor alcoholic beverage drinking were significantly related to GC risk. The case-control differences tended to be consistent across geographic areas, despite marked regional variations in intake levels of certain foods. The high-risk areas tended to show higher consumption of food associated with elevated risk (traditional soups, cold cuts) and lower consumption of foods associated with reduced risks (raw vegetables, citrus fruits, garlic). Our findings indicate that dietary factors contribute to the regional variation of stomach cancer occurrence in Italy, and offer clues for further etiologic and prevention research.
Article
A case-control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric-cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency-matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric-cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric-cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric-cancer risk was related to whole-milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric-cancer risk and the age at which the interviewees started using refrigerators. This population-based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.
Article
A multicentric hospital-based case-control study was simultaneously performed in a high-risk and a low-risk area for stomach cancer in Germany, 143 patients with incident stomach cancer and 579 controls completing a retrospective interview about life style aspects. Periods of non-centralized water supply or well water as the only source compared to life-long central water supply, and preservation of meat by smoking it with spruce compared to no home smoking of meat, were significantly associated with an increased stomach cancer risk. Use of a refrigerator at home for 30 and more years compared to 24 years or less showed an inverse relationship, whereas salt intake estimated by questionnaire showed no relationship to stomach cancer risk. Tobacco smoking was negatively associated with risk for current smokers of cigarettes compared to non-smokers but was presumably not causally related. After adjustment for other food constituents, only increased vitamin C consumption showed an inverse relation to risk. For food groups, increased consumption of fruit, citrus fruit, cheese and whole-meal bread were associated with decreased risk. A similar effect was also seen for increased consumption of raw vegetables. Total vegetable consumption was not particularly associated with risk. Increased consumption of processed meat and of beer showed a positive association with risk whereas increased wine and liquor consumption showed a significant negative association. The association of alcoholic beverages with stomach cancer risk may reflect a particular life style rather than being causally related to risk.
Article
A multi-centre case-control study of diet and gastric cancer was carried out in 4 regions of Spain (Aragon, Castile, Catalonia and Galicia). We selected 354 cases of pathologically confirmed gastric adenocarcinoma from 15 hospitals, representative of nearly all those in the study areas. A control for each case, matched by age, sex and area of residence, was selected from the same hospital as the case. Habitual diet was investigated by the dietary history method, and past diet by means of frequency questionnaire. The results regarding consumption of food items are presented here. With respect to habitual diet, an increase in risk was associated with consumption of preserved fish, cold cuts and oleaginous fruits. A high intake of cooked green vegetables, fresh noncitrus fruit and dried fruit showed an inverse association with the risk of gastric cancer. Simultaneous intake of 2 groups of food which increase or decrease the risk of cancer strengthens the respective individual effect. The intake of protective food items seems to neutralize the effects of food items which increase risk. With reference to past diet, possible a protective effect was observed for daily consumption of fresh fruit and green vegetables.
Article
A case-control study involving interviews with 1,016 gastric cancer (GC) patients and 1,159 population-based controls in high- and low-risk areas was conducted to evaluate dietary factors and their contribution to the marked geographic variation in mortality from this cancer within Italy. Risks of GC were found to vary significantly with estimated nutrient in-take. Risk rose with increasing consumption of nitrites and protein, and decreased in proportion to intake of ascorbic acid, beta-carotene, alpha-tocopherol, and vegetable fat. The associations with nitrite and beta-carotene tended to fade, however, in multivariate analyses adjusting for intake of other nutrients. Ascorbic acid showed the strongest geographic gradient, with highest consumption in low-risk areas. The findings suggest that the protective effects we previously reported for consumption of fresh fruit, fresh vegetables and olive oil may be linked to the vitamins C and E contained in these foods. The findings are consistent with the hypothesis that N-nitroso compounds are involved in GC risks, since elevated risks were apparent for agents (nitrites, protein) that promote nitrosation, while decreased risks were found for nutrients (ascorbic acid and alpha-tocopherol) which inhibit the process.
Article
The neoplastic effects of administration of benzo[a]pyrene (BP) and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) by oral intubation to noninbred female Ha:ICR mice have been determined. Under the experimental conditions, BP induced papillomas of the forestomach. BP 7,8-dihydrodiol also induced papillomas of the forestomach and was more potent than BP. In addition, administration of BP 7,8-dihydrodiol caused a large number of pulmonary adenomas and lymphomas. Butylated hydroxyanisole (BHA) added to the diet at a concentration of 5 mg/g inhibited BP-induced neoplasia of the forestomach. BHA also inhibited neoplasia of the forestomach, lungs, and lymphoid tissues that was caused by administration of BP 7,8-dihydrodiol. These data suggest that the inhibitory effect of BHA on BP carcinogenesis may entail events that occur subsequent to the formation of BP 7,8-dihydrodiol.
Article
Subtypes of oesophageal and gastric cancer in Denmark are compared with respect to their occurrence in men and in women, and in the Danish capital, Copenhagen, versus the rest of Denmark. Three categories of tumours can be distinguished epidemiologically: oesophageal squamous carcinoma, oesophageal and cardial adenocarcinoma, and distal gastric cancer. Comparison of information reported to the Danish Cancer Registry and cause of death as indicated on death certificates suggests that considerable misclassification between subtypes of tumours occurs. The Danish experience supports the findings from other populations of increasing incidence of oesophageal and cardial adenocarcinoma, but because of possible changes in diagnoses over time and of misclassification of subtypes, the data must be interpreted with caution.
Article
In the framework of a nationwide case-control study of risk factors for stomach cancer, a household survey was conducted on those food habits at the family level which were considered relevant for stomach cancer. The practices of 741 case and 741 control households were compared and relative risks calculated by the unconditional maximum likelihood method. For each household, the person responsible for cooking completed the survey. Respondents to the household survey were 35% of the cases and 40% of the controls of the case-control study and otherwise other household members. Case households relied more frequently on their own gardens as a major source of vegetables and fruit, and they cooked their vegetables more often than control households. The vegetable and fruit consumption during the summer period per family member was significantly less in case households compared to control households. The difference in per capita vegetable and fruit consumption between case and control households persisted, but was considerably less pronounced when the consumption of the index person (case or control) was subtracted from the household consumption. The consumption of mainly wholemeal bread showed a relative risk (RR) of 0.18 (95% CI 0.07-0.44) compared with mainly white bread consumption, whereas frequent frying and stewing of meat was associated with an increased risk compared to boiling of meat (RR = 2.06, 95% CI 1.48-2.87). No association with risk was found for long-term refrigerator use or other storage modalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Stomach cancer mortality was prospectively studied among 9753 Japanese men and women who first responded to a mailed questionnaire in 1985 and were then followed through May 31, 1991. During this follow-up period, 57 stomach cancer deaths were identified. Current smokers had an increased risk of deaths from stomach cancer compared with never smokers (relative risk (RR) = 2.29, 95% confidence interval (CI): 1.15-4.56), but there was no dose-response to amount of cigarettes smoked. Daily alcohol drinkers who consumed 50 ml or more of alcohol per day also had a greater risk than nondrinkers (RR = 3.05, 95% CI: 1.35-6.91). There was no association between stomach cancer mortality and individual food consumption except a positive association with fruit intake. However, frequent use (greater than or equal to 3-4/week) of broiling of meats and traditional style Japanese salad preparation in their cooking procedures were positively associated with stomach cancer mortality. The RR values compared with infrequent use (less than or equal to 1-2/month) were 2.27 (95% CI: 1.06-4.85) and 3.10 (95% CI: 1.40-6.85), respectively. A positive family history of cancer, especially stomach cancer, significantly increased the risk of stomach cancer deaths (RR = 2.01, 95% CI: 1.12-3.63). The effects of these variables remained after adjustment for other variables.
Article
The epidemiologic literature on the relationship between vegetable and fruit consumption and human cancer at a variety of sites is reviewed systematically. A total of 13 ecologic studies, nine cohort studies, and 115 case-control studies are included. Cancer of all sites, cancers of lung, breast, colon, rectum, esophagus, larynx, oral cavity and pharynx, stomach, pancreas, prostate, bladder, ovary, endometrium, cervix, and thyroid, as well as mesothelioma and gestational trophoblastic disease, are considered. Relevant data from clinical trials, animal, and in vitro studies are included. It is concluded that consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites. The association is most marked for epithelial cancers--particularly those of the alimentary and respiratory tracts--and, currently, is weak to nonexistent for hormone-related cancers. The association exists for a wide variety of vegetables and fruit with some suggestion that raw forms are associated most consistently with lower risk. Possible mechanisms by which vegetable and fruit intake might alter risk of cancer and possible adverse effects of vegetable and fruit consumption will be considered in Part II of this review.
Article
The associations between methods of cooking meats and colorectal cancer were examined in a population-based case-referent study performed in Stockholm in 1986-1988. The study included 559 cases and 505 referents. Total meat intake, frequent consumption of brown gravy, and a preference for a heavily browned meat surface each independently increased the risk for colorectal cancer. The relative risks (RR) were higher for rectal than for colon cancer, and for boiled meat (RR colon = 1.7, RR rectum = 2.7) than for meat fried with a medium or lightly browned surface (RR colon = 0.8, RR rectum = 1.1), but the highest risks were for meat fried with a heavily browned surface (RR colon = 2.8, RR rectum = 6.0). The analyses were adjusted for year of birth, gender and fat intake. Further adjustments for total energy, dietary fiber intake, body mass and physical activity had little or no influence on the results. The findings suggest that, in addition to frequent meat intake, a heavily browned meat surface formed when frying meat at high temperatures is important in the etiology of colorectal cancer.
Article
Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer. In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach. Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women. By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites. The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.
Article
Mutagenic heterocyclic amines in cooked foods were carcinogenic to mice, rats and/or monkeys, when they were given orally continuously. The most common target organ was the liver, but in CDF1 mice lung tumors, forestomach tumors, lymphomas/leukemias, and blood vessel tumors in the brown adipose tissues were also induced. In F344 rats, in addition to liver tumors, tumors in the Zymbal gland, skin, clitoral gland, small and large intestines, oral cavity, and mammary gland were also induced. Monkeys given IQ developed metastatic hepatocellular carcinomas.
Article
Potent mutagenic activity in Salmonella bacteria has been reported in cooked foods in numerous laboratories worldwide. Determining the human risk from exposure to these biologically active compounds in our diet requires genotoxic and carcinogenic evaluation of the chemicals coupled with determination of the dose consumed. Thus, knowledge of the exact structure of the mutagens present in the food and enough synthesized material for biological assessment are essential for this evaluation. To reach this goal, isolation of these compounds requires the Ames/Salmonella assay to guide the purification and identification process. Mass and NMR spectrometry are used to identify the isolated compounds. Finally, these findings are followed by synthesis of the exact isomer. The predominant class of mutagens found in cooked foods of the western diet are amino-imidazo-quinoxalines, amino-imidazo-pyridines and amino-imidazo-quinolines, collectively called amino-imidazoazaarenes (AIAs). Mass amounts of these specific compounds range from less than 1 to 70 ng/g of meat. The mutagens are formed from the heating of natural precursors (creatinine, amino acids, and possibly sugars) in the food. These AIAs are some of the most potent mutagens ever tested in Salmonella bacteria with the number and position of methyl groups having an important influence on the mutagenic activity.
Article
A reduced questionnaire was developed by successively omitting segments of the full (98-item) Block questionnaire and calculating the correlations between nutrient estimates produced by the full and reduced versions. The reduced version contains 60 food items and requires 17 minutes to administer by an interviewer. It is intended to capture all nutrients in the diet, as is the full version. The reduced version was validated against three four-day records in a group of middle-aged women, and against two seven-day records collected 10-15 years ago in a group of older men. The absolute value of macronutrients estimated by the reduced questionnaire was lower than food-record estimates, but most micronutrients were not underestimated. For macronutrients correlations with food records were slightly lower with the reduced questionnaire, but for micronutrients there was only slight or no reduction in correlations as a result of using the reduced version. The brief version may be useful in studies that cannot allow the 30-35 minutes required for the full-length questionnaire.
Article
Data in a regional cancer registry covering a population of 5 million and with an efficiency of registration of over 95% have been used to examine incidence trends in oesophageal and gastric carcinoma. In the West Midlands Region of the UK, during the period 1962 to 1981 the age standardised incidence of gastric carcinoma decreased by 20%. However, an analysis by both histological type and detailed site reveals that while the incidence of distal lesions is diminishing, the incidence of adenocarcinoma of the oesophagus and cardia is increasing. The proximal and distal lesions also exhibit marked differences in social class distribution and sex ratio. The results strongly suggest that the aetiological factors involved for cardia and adjoining sites are different from those for pyloric antrum.
Article
We examined the nutritional epidemiology of gastric cancer in 293 cases and neighborhood-, age-, and sex-matched controls in communities throughout the counties of Niagara, Monroe, and Erie in western New York. The interview was highly detailed, requiring two and one-half hours to complete; it attempted to provide an estimate of total calories ingested as well as of macro- and micronutrients and behaviors that could affect alimentary exposures, such as the use of refrigeration. We found that risk was enhanced by sodium, fat, and retinol. Substantial reductions in risk were associated with ingestion of carotene, especially raw vegetables (including celery, cucumbers, carrots, green peppers, tomatoes, and onions), as well as with increased use of low-temperature food storage. Both refrigeration and carotene could inhibit oxidation products that could act as carcinogens in the stomach.
Article
A case-control study involving interviews with 137 incident male cases of stomach cancer under the age of 55 yr and an equal number of age- (within 5 yr), race-, and sex-matched neighborhood controls in Los Angeles County was conducted. Cases were more likely to be foreign born and had less education compared with controls. Any use of tobacco products conferred a 2-fold increase risk for stomach cancer; the effect was present in all subsites: the cardia; fundus/body; and antrum/pylorus. Weekly use of alcoholic beverages was also a risk factor, but the effect was not observed in the antrum/pylorus. In comparison with controls, cases had a significantly higher intake of beef (cardia only) and barbecued/smoked foods, had a lower intake of fresh fruits/vegetables, and were more likely to prefer white than whole grain bread. Occupational exposure to metal dust was associated with a 70% increased risk of stomach cancer, with an increase in risk as the duration of exposure increased. This association was most pronounced for tumors in the antrum and pylorus. Subjects with a history of stomach or duodenal ulcer showed a 2-fold increased risk of stomach cancer. The effects of smoking, alcohol, intake of white bread, history of ulcer, and exposure to metal dust remained statistically significant when these variables were examined simultaneously in multivariate analyses and when the multivariate analyses were confined to directly interviewed subjects.
Article
Both descriptive and analytical studies were carried out to examine epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan. The age-adjusted mortality rate of stomach cancer has been decreasing since the early 1970s for both males and females. The male-to-female ratio of the disease has remained around 2:1 in the past three decades. Comparison of the incidence of stomach cancer among Chinese in different countries showed a much lower incidence among Chinese in the USA than those in southeastern Asia. A hospital-based matched case-control study carried out in Taipei metropolitan areas showed a positive association of stomach cancer with blood type A, chronic gastric diseases, cigarette smoking, alcohol drinking, green tea drinking as well as consumption of salted meat, cured meat, smoked food, fried food and fermented beans. There was also a significant negative association between the disease and the consumption of milk.
Article
A case-control study of diet and stomach cancer was conducted during 1979-1982 in Toronto, Winnipeg, and St. John's Canada. Two hundred forty-six histologically verified cancer cases were individually matched by age, sex, and area of residence to 246 randomly selected population controls. Daily nutrient consumption values were calculated from quantitative diet history questionnaire data through use of the US Department of Agriculture Food Composition Data Bank, which was extended and modified for Canadian items. For the analysis, continuous conditional logistic regression methods were used. It was found that consumption of dietary fiber was associated with decreased risk of gastric cancer; the odds ratio estimate of trend was 0.40/10 g average daily intake of fiber (i.e., 0.40(1.5)/15 g, etc.) (p less than 10(-8)). Also, average daily consumption of nitrite, chocolate, and carbohydrate was associated with increasing trends in risk, with odds ratio estimates, respectively, 2.6/mg (p less than 10(-4)), 1.8/10 g (p less than 10(-4)), and 1.5/100 g (p = 0.015). While citrus fruit intake appeared to be somewhat protective (odds ratio = 0.75/100 g daily average, p = 0.0056), vitamin C intake was less so, and vitamin E not at all. Thus, a number of dietary components seem to be implicated in the pathogenesis of stomach cancer.
Article
Carcinogenicities of mutagenic heterocyclic amines in cooked foods have been tested in CDF1 mice and F344 rats of both sexes. Eight heterocyclic amines--Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeA alpha C, A alpha C, IQ, and MeIQ--were given to mice and/or rats at 0.02 to 0.08% in the diet continuously. In mice, all heterocyclic amines tested were demonstrated to be carcinogenic. Hepatocellular carcinomas were induced in a high incidence in all groups treated with heterocyclic amines. Hemangioendothelial sarcomas were also induced by Glu-P-1, Glu-P-2, MeA alpha C, and A alpha C. Most hemangioendothelial sarcomas were located in the interscapular brown adipose tissue. In mice given IQ, forestomach and lung tumors were also observed in a high incidence. Carcinogenicity tests on MeIQ are ongoing, and interim data by week 83 show that MeIQ also induces forestomach tumors in addition to liver tumors. In rats, hepatocellular carcinomas were induced by Trp-P-1, Glu-P-1, Glu-P-2, and IQ. In rats given Glu-P-1, Glu-P-2, and IQ, adenocarcinomas in the small and large intestines, squamous cell carcinomas in the Zymbal gland and clitoral gland were also observed in a high incidence.
Article
In south Louisiana, 391 recently diagnosed gastric cancer patients and an equal number of controls were interviewed. Questions asked covered residential and occupational histories, environmental exposures, tobacco use, diet, alcohol consumption, and pertinent demographic characteristics. Elevated relative risks were found for use of tobacco and alcohol products. Diet was found to be the main determinant of gastric cancer risk in south Louisiana. Both dietary patterns and dietary risk factors differed for blacks and whites, although fruits as a group and dietary vitamin C were found to exert strong protective effects for both blacks and whites. Consumption of smoked foods and homemade or home-cured meats increased risk of gastric cancer for blacks but not for whites. The findings are discussed in the light of the prevailing etiologic hypotheses.
Article
A recently completed case-control study in the Minneapolis-St. Paul area using population-based living controls and dead controls afforded the opportunity to compare these two control groups on their exposure histories. Detailed information was obtained by interview from 697 living controls and the next of kin of 493 dead controls. The dead controls of both sexes were reported to have been significantly heavier cigarette smokers compared with living controls, as well as heavier consumers of hard liquor, beer, and drugs, and to have had more adulthood diseases. There were no consistent differences between the control groups for consumption of nonalcoholic beverages, some aspects of diet, ethnic and religious background, usual occupation, and residential history. It appears that exposures associated with premature death are overrepresented in dead controls compared with living controls, while those variables not associated with premature mortality are distributed more or less similarly between the two groups.
Article
The author compared medical, smoking, and dietary consumption data obtained from cases or controls and their respective next-of-kin as part of a study of colon cancer in the five Pennsylvania counties of the Philadelphia metropolitan area. The case population consisted of whites aged 45-69 years who had resided in the region for at least two years prior to diagnosis and diagnosed with colon cancer after July 1, 1976. Controls were selected using an area probability sampling scheme and were frequency-matched to the case group. Questionnaires for cases and controls were administered by interviewers; questionnaires for their next-of-kin were randomly allocated to be self- or interviewer-administered. Agreement when both respondents received the interviewer-administered questionnaire was greater than when the next-of-kin received the self-administered questionnaire for all variables. Medical and cigarette smoking variables exhibited high agreement, the percentage agreement exceeded 80 for 80% of the comparisons, the kappa statistic exceeded 0.6 for 54% of the comparisons. Diet histories were more variable (average agreement ranging from 54% to 82% and average kappa values from 0.17 to 0.59). A subanalysis of subjects and spouses showed that husbands and wives gave equally reliable responses.
Article
One hundred and sixty male patients and 68 female patients with gastric cancer at Roswell Park Memorial Institute were matched with control patients with no neoplastic or gastrointestinal disease on age, country of birth, and nationality background of parents and grandparents. The matching was accomplished to control socioeconomic factors previously found related to gastric cancer. Item-by-item analysis of diet for both sexes showed that patients more frequently ingested potatoes, ate lettuce less often, ate more irregularly, and used cathartics frequently. Because diets typically do not consist of single items of food, using scaling techniques, we attempted to distinguish differences between cases and controls in frequency of use of groups of foods previously hypothesized to be related to the disease. We found no relationships on: 1. duration of use of the several fats used in frying; 2. frequency of ingestion of the various foods consumed fried, considered separately or together, weighting for the number used and the frequency of each; 3. frequency of eating all meats and fish considered separately or together, and 4. frequency of use of the various alcoholic beverages. We found a rather substantial difference in eating vegetables raw. Control patients ate larger numbers of vegetables raw than cancer patients. Low risk of gastric cancer was associated with ingesting in the uncooked state lettuce, tomatoes, carrots, coleslaw, and red cabbage, and risk declined with increases in the number of these vegetables eaten raw.
Article
A case-control study of esophageal cancer was conducted among the black male residents of Washington, D.C., to find reasons for the exceptionally high risk in this population. The next of kin of 120 esophageal cancer cases who died during 1975-77 and of 250 D.C. black males who died of other causes were interviewed. Five indicators of general nutritional status--fresh or frozen meat and fish consumption, dairy product and egg consumption, fruit and vegetable consumption, relative weight (wt/ht2), and number of meals eaten per day--were each significantly and inversely correlated with the relative risk of esophageal cancer. Associations with other food groups were not apparent. The least nourished third of the study population, defined by any of these five measures, was at twice the risk of the most nourished third. None of these associations was markedly reduced by controlling for ethanol consumption, the other major risk factor in this population; smoking; socioeconomic status; or the other nutrition measures. When the three food group consumption measures were combined into a single overall index of general nutritional status, the relative risk of esophageal cancer between extremes was 14. Estimates of the intake of vitamin A, carotene, vitamin C, thiamin, and riboflavin were inversely associated with relative risk; but each micronutrient index was less strongly associated with risk than were the broad food groups that provide most of the micronutrient. Thus no specific micronutrient deficiency was identified. Instead, generally poor nutrition was the major dietary predictor of risk and may partially explain the susceptibility of urban black men to esophageal cancer.
Article
Recently published data suggest relationships between ingestion of a number of food items and risk of cancer of the stomach, bowel and mouth. This engenders concern over the accuracy of such data. To study this, dietary interviews of 158 males in the Western New York Study of Cancer Epidemiology are compared to their spouses' estimates of the husband's dietary histories as taken in separate interviews. Respondents were asked to estimate the frequency with which the males consumed each of several foods. For analysis, the frequency estimates were assembled into categories similar to those used in recent epidemiologic analysis: 5-7 times per week, 1-4 times per week, 1-3 times per month and less than once per month. Generally, 60-80% of respondents pairs agree exactly on the frequency of consumption for individual food items. Over 90% of spouse and respondent food frequency estimates are within one frequency category of each other. Radical disagreements between spouses are rare; generally, in less than 2% of spouse pairs does one member estimate the maximum frequency category, and the other minimum frequency category. The authors suggest therefore that, although diet histories are not precisely replicable, they must be adequate to reveal gross differences between cases and controls.
Article
In case-control studies with three exposure levels where disease risk is associated with exposure, the direction of bias in the odds ratios (ORs) from nondifferential misclassification depends on the risk level, misclassification rates, and exposure distributions. To extend these generalizations, we present a graphical analysis of bias from nondifferential misclassification assuming linear and nonlinear monotonic increasing exposure-risk patterns. In both middle and upper exposure levels, bias is usually toward the null, increasing in magnitude as the misclassification rates increase and as the skewness of the exposure distribution increases. In the middle exposure level, bias away from the null may occur when the misclassification rate is low in the reference level and moderate to high in the upper exposure level, and risk increases with exposure. Bias away from the null does not occur in the upper exposure level. In both excess risk levels, crossover bias (that is, a reversal of the OR) may occur when exposure classification is worse than chance. The magnitude of bias away from the null is constrained by the unbiased OR of the upper exposure level, whereas that of crossover bias is constrained by the inverse of the unbiased OR of the upper exposure level.
Article
Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, we estimated the average intakes of HAs, based on analyses of the concentrations of HAs in cooked foods and data from a dietary survey of the US population and quantified the cancer potencies of the individual compounds using dose–response data from animal bioassays. Measured concentrations of HAs in cooked foods were taken from a major review of the open literature. Only those concentrations that were associated with normal cooking conditions were chosen for use in estimating dietary intakes. The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989. Dietary intakes of the five principal HAs in descending order were 2-amino-l-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (AαC) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) > 2-amino-3,4,8-trimethyllmidazo[4,5-f]quinoxa-line (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > AαC. An upper-bound estimate of the incremental cancer risk is 1.1×10−4, using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (˜80%) to total risk.
Article
Information on the etiology of esophageal cancer in lifelong nonsmokers is of interest to understand and quantify risk factors for the disease in the absence of the residual confounding by tobacco. Of a total of 316 cases with histologically confirmed incident cancers of the esophagus, 46 (17 males and 29 females) who described themselves as lifelong nonsmokers were selected to assess esophageal cancer risk in the absence of potential confounding and interactive effects of smoking. These patients were compared to 230 lifelong nonsmoker controls (85 males and 145 females) admitted to hospital for acute, nonneoplastic, non-alcohol-related conditions. The major risk factor for cancer of the esophagus in lifelong nonsmokers was elevated alcohol consumption: compared to drinkers of fewer than 4 drinks per day the relative risk (RR) was 2.7 (95% confidence interval, 1.1-6.8) for 4 to fewer than 8 drinks, and 5.4 (95% confidence interval, 1.4-21.0) for 8 or more drinks, with a significant trend in risk. Among selected indicator foods considered, significant protective effects were observed for fish (RR = 0.5 for the highest consumption tertile), green vegetables (RR = 0.6), and fresh fruit intake (RR = 0.3). Consequently, there was a significant inverse relationship with an estimate of beta-carotene intake (RR = 0.5 and 0.4, respectively, for the middle and highest tertiles of intake versus the lowest), with a significant trend in risk. The estimated RR for the highest alcohol consumption and lowest beta-carotene intake category was 8.6, and these two factors together explained over 45% of cases. Gastrectomy and family history of cancer of the esophagus were also associated with increased risk (RR = 4.6 and 4.3, respectively).
Article
It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.
Article
Esophageal cancer displays unique epidemiologic features that distinguish it from all other malignancies. It shows marked geographic variation both internationally, with exceptionally high rates (some of the world's highest for any cancer) in limited areas of Asia, and nationally, with clustering of increased rates within the United States as well. However, the patterns are changing with rates of squamous cell carcinomas decreasing and adenocarcinomas increasing rapidly in several western countries. The causes of the clusters of squamous cell carcinomas in parts of Asia and Africa are not well known, but within the United States and other western countries, tobacco and alcohol consumption are the major determinants. Nutritional factors also may play a major role, with diets high in fresh fruits and vegetables consistently associated with reduced risks. The causes of the rapidly increasing rates of adenocarcinomas of the esophagus, and reasons or its occurrence primarily among white men, are enigmatic. Additional research on the etiology of this emerging cell type is warranted, and may provide information crucial to the development of readily implementable preventive strategies.