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Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date, different food sources of fiber have not been examined with respect to noncardia tumors or diverse histologic sub-types. This study prospectively examines associations between fiber from different food sources and incident gastric adenocarcinomas (GC) among more than 435,000 subjects from 10 countries participating in the European Prospective Investigation into Cancer and Nutrition study. Subjects aged 25-70 years completed dietary questionnaires in 1992-98, and were followed up for a median of 6.7 years. About 312 incident GCs were observed. The relative risk of GC was estimated based on cohort-wide sex-specific fiber intake quartiles using proportional hazards models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Intakes of cereal fiber, but not total, fruit or vegetable fiber, were associated with reduced GC risk [adjusted HR for the highest vs. lowest quartile of cereal fiber 0.69, 0.48-0.99]. There was a strong inverse association for diffuse [HR 0.43, 0.22-0.86], but not intestinal type [HR 0.98, 0.54-1.80] tumors. Associations for cardia vs. noncardia tumors were similar to those for overall GC, although cardia associations did not reach significance. Cereal fiber consumption may help to reduce risk of GC, particularly diffuse type tumors. Further study on different food sources of fiber in relation to GC risk is warranted to confirm these relationships.

OBJECTIVE: Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer. METHODS: Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors. RESULTS: During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate. CONCLUSION: This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and - and -tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and -tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma -cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, Ptrend=0.005) and lipid-unadjusted -tocopherol (OR=0.59, 95% CI=0.37-0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted -tocopherol (OR=0.26, 95% CI=0.11-0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and -tocopherol are associated with reduced risk of GC.

Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.

RIVM rapport:Een op de 5 mannen en een op de 8 vrouwen in de leeftijd van 20-59 jaar heeft een verhoogde bloeddruk, terwijl ongeveer een op de 10 mannen/vrouwen een te hoog cholesterolgehalte heeft. Bijna de helft van de mannen en ongeveer een derde van de vrouwen heeft overgewicht. Risicofactoren voor chronische ziekten komen over het algemeen vaker voor bij mannen dan bij vrouwen, vaker bij ouderen dan bij jongeren en vaker bij lager opgeleiden dan bij hoger opgeleiden. Overgewicht komt bijvoorbeeld bij laag opgeleiden 3 keer (mannen) tot 5 keer (vrouwen) vaker voor dan bij hoog opgeleiden.Dit blijkt uit het MORGEN-project, een grootschalig onderzoek dat in de periode 1993-1997 is uitgevoerd onder 23.000 mannen en vrouwen uit Amsterdam, Doetinchem en Maastricht. In het project is informatie verzameld over (veranderingen in) risicofactoren voor chronische ziekten, zoals hart- en vaatziekten, diabetes, astma, COPD en gewrichtsaandoeningen. Deelnemers vulden vragenlijsten in over leefgewoonten (roken, voeding, bewegen) en gezondheid, en ondergingen een lichamelijk onderzoek waarbij lengte, gewicht, bloeddruk en longfunctie werden gemeten en waarbij bloed werd afgenomen waarin het totaal- en HDL-cholesterolgehalte en glucosegehalte werden bepaald. Bij een deel van de oudere deelnemers (45 jaar en ouder) werd ook een aantal cognitieve testen afgenomen. Het onderzoek geeft een goed beeld van de situatie in Nederland ten aanzien van risicofactoren voor chronische ziekten. De gegevens zijn een belangrijke bron gebleken voor onderbouwing van het Nationaal Kompas Volksgezondheid en het Chronische Ziekten Model van het RIVM. In dit rapport worden voor de genoemde risicofactoren en chronische ziekten de prevalentie en trend beschreven, naar leeftijd, geslacht en opleiding., One out of 5 men and one out of 8 women aged 20-59 years have high blood pressure, while about one out of 10 men and women has a high total cholesterol level. About half the men and one-third of the women are overweight. Chronic disease risk factors are more prevalent among men vs. women, among the elderly vs. the youth, and among the lower educated vs. the higher educated. Prevalence of overweight for example, was 3 times (men) to 5 times (women) higher in lower educated individuals than in the higher educated. These represent a few of the results of the MORGEN project, a large-scale monitoring project carried out between 1993 and 1997 among 23,000 men and women living in Amsterdam, Doetinchem and Maastricht. Data were collected on (changes in) chronic disease risk factors, such as cardiovascular diseases, diabetes, asthma, COPD and musculoskeletal disorders. Respondents filled in questionnaires on lifestyle habits (smoking, diet and physical activity) and health, and underwent a physical examination in which height, weight, blood pressure and lung function were measured. They supplied blood samples in which serum total cholesterol, HDL cholesterol and non-fasting glucose were determined. A subsample of respondents aged 45 years and older underwent a series of cognitive tests. This project has proven to be a valuable source of information on chronic disease risk factors in (subgroups of) the general Dutch population. It has contributed to the National Public Health Compass and RIVM's Chronic Disease Model. Prevalence of and trends in the risk factors and chronic diseases according to age, gender and educational level are reported here.

RIVM rapport:Dit rapport beschrijft de opbouw en en het gebruik van de biobank van de RIVM-centra CVG en PZO. Deze biobank is voor het grootste deel opgebouwd tussen 1987 en 1998 in het kader van drie grootschalige epidemiologische projecten. De deelnemers (ca. 60 000) aan deze projecten hebben bloed afgestaan, dat is opgeslagen in vriezers van -20 graden Celsius, -86 graden Celsius en -196 graden Celsius. Het bloed is verdeeld in fracties (plasma, serum, witte bloedcellen, rode bloedcellen) en opgeslagen in porties van 0,5 ml en 1,5 ml. Het bloed is al voor verschillende onderzoeksvraagstellingen op gebied van chronische ziekten gebruikt, waarbij het bloed van het oudste project het meest is uitgeput. Ook is er DNA opgewerkt. Om bloed veilig te stellen voor onderzoek naar specifieke chronische ziekten of andere kenmerken zijn er zogenaamde beschermde cohorten ingesteld. Op dit moment zijn er vier beschermde cohorten: hart- en vaatziekten, kanker, migraine, en overleden deelnemers., This report describes the structure and use of the biobank at the RIVM Centres for Nutrition and Health, and Prevention and Health Services Research. Samples for this biobank were collected mainly between 1987 and 1998 for three large-scale epidemiological projects. The blood samples of approximately 60,000 participants were stored at temperatures of -20 degrees Centigrade, -86 degrees Centigrade and -196 degrees Centigrade, with samples divided into fractions (plasma, serum, white blood cells, red blood cells) and stored in 0.5 ml and 1.5 ml vials. These samples have been used for several research projects in the field of chronic diseases. In order to regulate the use of the samples for research into specific chronic diseases, so-called protected cohorts have been imposed. At the moment there are four: cardiovascular diseases, cancer, migraine and deceased participants.

RIVM rapport:In dit onderzoek zijn dieten bestudeerd die rijk waren aan flavonoiden en thee-extracten. Hiervan is onderzocht in hoeverre deze bescherming bieden bij het ontstaan van huidtumoren en tumoren ontwikkeld in de dunne en dikke darm. Daarnaast is onderzocht of deze dieten en extracten bescherming geven aan het immuunsysteem. De resultaten geven aan dat deze dieten en thee-extracten geen duidelijke anticarcinogene werking hadden, maar dat zij in alle gevallen wel bescherming boden aan de UV geinduceerde immuunsuppressie in de huid. De anticarcinogene werking van thee op dunne en dikke darm tumoren als gevolg van een mutatie in het APC gen is aanleiding tot verder onderzoek., In this study flavonoid-rich diets and tea extracts were investigated. These diets were studied for their putative protective effect on UV induced skin tumors and tumors in the small intestine and colon. Moreover , the same diets were studied in UV induced immunosuppression. The results show that these diets and tea extracts did not consistently have anticarcinogenic properties, but that they gave protection against UV-induced immunosuppression in the skin in all experiments. The carcinogenic activity of tea on the small intestine and colon tumors, due to a mutation in the APC gene, will be further investigated.

RIVM rapport:In het onderzoeksproject Monitoring Risicofactoren en Gezondheid in Nederland (het "MORGEN-project") wordt de gezondheidssituatie en het voorkomen van risicofactoren gemeten in een steekproef van de Nederlandse bevolking gedurende de periode 1993 tot en met 1997. In het onderzoeksjaar 1997 zijn circa 3900 mannen en vrouwen in de leeftijd van 20-59 jaar onderzocht door de GGD'en in Amsterdam, Doetinchem en Maastricht. Bij deze personen werden onder meer bloeddruk, gewicht en lichaamsomtrek gemeten, bloed afgenomen (voor totaal en HDL-cholesterol en glucose) en de longfunctie bepaald. Tevens werden een aantal vragen afgenomen. De geschatte prevalentie van diabetes mellitus op grond van de nieuwe Amerikaanse richtlijnen is 4%. Hypertensie komt voor bij circa 8% van de mannen en 6% van de vrouwen. Ernstig overgewicht (obesitas) komt bij 8% van de mannen en 10% van de vrouwen voor. Een te hoog cholesterolgehalte komt voor bij ruim 8% van de respondenten. Het percentage sigarettenrokers was 41% bij mannen en 35% bij vrouwen. Inactiviteit tijdens de vrije tijd werd gerapporteerd bij ruim 40%. Het percentage volwassenen met overgewicht, hypertensie of een te hoog cholesterol en het percentage volwassenen dat rookt is daarmee vergelijkbaar met de percentages van 1996., The Monitoring Project on Risk Factors for Chronic Diseases (MORGEN-project) is conducted by the National Institute of Public Health and the Environment (RIVM). Its general purpose is to determine the prevalence of risk factors for chronic diseases as well as the prevalence of some specific chronic conditions in a sample of the general population. In 1997 approximately 3900 men and women aged 20-59 years were examined in three towns in the Netherlands (Amsterdam, Doetinchem and Maastricht). According to guidelines of the American Diabetes Association then, the prevalence of diabetes mellitus was about 4%. Hypertension was present in 8% of the men and 6% of the women. Of the men, 8% were obese and of the women 10% were obese. Hypercholesterolemia occurred in 8%. The prevalence of smoking was 41% in men and 35% in women. Inactivity during leisure time was reported in over 40% of the participants. Prevalence of hypertension, obesity and hypercholesterolemia, as well as smoking, were comparable to the prevalence in 1996.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.

RIVM rapport:Het project Monitoring Risicofactoren en Gezondheid in Nederland (het "MORGEN-project") is een onderzoeksproject van het Rijksinstituut voor Volksgezondheid en Milieu (RIVM), waarin de gezondheidssituatie en het voorkomen van risicofactoren worden gemeten in een steekproef van de Nederlandse bevolking gedurende de periode 1993 tot en met 1997. Dit verslag betreft de resultaten van het onderzoeksjaar 1995. Het onderzoek werd uitgevoerd bij 20 tot 59-jarige mannen en vrouwen in Amsterdam en Maastricht. In Doetinchem werden de deelnemers van het Peilstationsproject Hart- en Vaatziekten in 1988, inmiddels 26 tot 65 jaar oud, opnieuw onderzocht., The Monitoring Project on Risk Factors for Chronic Diseases (MORGEN-project) is conducted by the National Institute of Public Health (RIVM). Its general purpose is to determine the prevalence of risk factors for chronic diseases as well as the prevalence of some specific chronic conditions in a sample of the general population.

RIVM rapport:Op basis van epidemiologisch en (dier)experimenteel onderzoek is reeds langer bekend dat de meest voorkomende vormen van humane kanker waarschijnlijk te wijten zijn aan levensstijl factoren (inclusief voedingsgewoontes), in combinatie met genetische factoren die verantwoordelijk zijn voor individuele verschillen in gevoeligheid. Daarnaast heeft dit onderzoek meer recent ook geleid tot de identificatie (of postulatie) van een aantal (klassen van) stoffen, met name in de voeding, waaraan een beschermende werking tegen kanker kan worden toegeschreven. Stoffen die kanker veroorzaken worden carcinogene stoffen genoemd terwijl de tegen kanker beschermende stoffen als anticarcinogeen worden aangeduid. Dit zijn bijvoorbeeld vitamine C, beta-caroteen en vezels, maar ook non-nutrienten zoals bijvoorbeeld flavonoiden. Ten aanzien van deze beschermende stoffen is tot op heden nog weinig bekend over de rol en het belang van de afzonderlijke componenten, over hun mogelijke werkingsmechanismen en over mogelijke synergistische of antagonistische effecten ervan. In dit rapport wordt een beknopt overzicht gegeven van het mechanisme van de tumorontwikkeling en de mogelijke werking van carcinogene stoffen en anticarcinogene stoffen hierop. Tevens wordt de epidemiologische kennis over voeding en kanker, met name de beschermende effecten van groenten en fruit, samengevat. Aan de hand hiervan worden voorstellen gedaan voor verder onderzoek in het RIVM op het gebied van de anticarcinogenese die nauw aansluiten bij de reeds lopende projecten en de aanwezige expertise. Gezien de huidige lacunes in de wetenschappelijke kennis op dit terrein omvat dit: (i) bepalen van de antimutagene werking (in vitro systemen ; AMES test), immunomodulerende effecten van potentiele anticarcinogene verbindingen (voorlopig o.a. flavonoiden), (ii) het uitvoeren van anticarcinogeniteits studies in proefdieren met specifieke aandacht voor colon- en huidtumoren (iii) op basis van het voorafgaande het ontwikkelen van, Epidemiologic studies and animal experiments have shown that the most common forms of human cancer are related to life-style factors (including dietary habits) in combination with genetic factors that influence the susceptibility of individuals to these life-style factors. Recent research has also led to the identification (or postulation) of a number of compounds or classes of compounds, largely of dietary origin, which may prevent the development of cancer. In contrast to the so-called carcinogens which enhance tumor development, these inhibitory compounds are referred to as anticarcinogens. Anticarcinogens comprise not only (micro)nutrients such as vitamin C, beta-carotene and dietary fibers, but also non-nutrients such as flavonoids. Only little is known about the importance and the function of specific compounds, their mechanisms of action and possible synergistic or antagonistic effects. In the present report a short overview on the mechanisms of tumor development and the potential enhancing effects of carcinogens and inhibitory effects of anticarcinogens will be presented. In addition the available epidemiologic evidence on diet and cancer, with emphasis on the protective effects of vegetables and fruits, will be briefly summarized. Based on these summaries, perspectives for future research on anticarcinogenesis will be discussed, which are closely related to ongoing projects at RIVM. In view of the gaps in our knowledge, this comprises the following aspects: (i) determination of the antimutagenic activities (in vitro tests ; AMES test), modulation of immune functions by specific potential anticarcinogens (e.g. flavonoids), (ii) in vivo animal experiments to determine anticarcinogenic activities, with special emphasis on skin and colonic tumors, (iii) development of different biomarkers that can be applied in epidemiologic studies. The RIVM is also involved in epidemiological research like the EPIC cohort study on diet and cancer which will provide informatio

RIVM rapport:Het project Monitoring Risicofactoren en Gezondheid in Nederland (het "MORGEN-project") is een onderzoeksproject van het Rijksinstituut voor Volksgezondheid en Milieu (RIVM), waarin de gezondheidssituatie en het voorkomen van risicofactoren wordt gemeten in een steekproef van de Nederlandse bevolking gedurende de periode 1993 tot en met 1997. Dit verslag betreft de resultaten van het onderzoeksjaar 1994. Het onderzoek werd uitgevoerd bij 20 tot 59-jarige mannen en vrouwen in Amsterdam en Maastricht. In Doetinchem werden de deelnemers van het Peilstationsproject Hart- en Vaatziekten in 1988, inmiddels 26 tot 65 jaar oud, opnieuw onderzocht., The Monitoring Project on risk factors for chronic diseases (MORGEN-project) is conducted by the National Institute of Public Health (RIVM). Its general purpose is to determine the prevalence of risk factors for chronic diseases as well as the prevalence of some specific chronic conditions in a sample of the general population.

RIVM rapport:Dit rapport gaat over populatie attributieve risico's (PAR's) die de bijdrage van verschillende risicofactoren (leefstijlfactoren, zoals roken, alcoholconsumptie, lichamelijke activiteit, en voeding, alsmede biologische factoren, zoals totaal serum cholesterol, HDL-cholesterol, bloeddruk, glucosetoleratie, en lichaamsgewicht naar lengte) aan mortaliteit ten gevolge van een aantal ziekten (coronaire hartziekten, beroerte, CARA, diabetes, en sommige vormen van kanker) kwantificeren. Relatieve risico's en prevalenties van risicofactoren zijn nodig om PAR's te berekenen. Relatieve risico's zijn ontleend aan de internationale literatuur en prevalenties van risicofactoren (voornamelijk in de leeftijdsklasse van 20-59 jaar) zijn ontleend aan het MONITORING project 1987-1991. In hoofdstuk twee worden belangrijke aannamen en problemen voor het berekenen van PAR's en PAR-achtige maten uiteengezet. Hoofdstuk drie bevat een beschrijving van PAR berekeningen voor een aantal determinanten, later samengevat in hoofdstuk vier vanuit het perspectief van zowel ziekten als determinanten. PAR's voor individuele determinanten varieerden van 10 tot 90%. Vanuit volksgezondheidsperspectief levert ingrijpen in een determinant met een matige tot grote invloed op een of vaak voorkomende ziekten, meer winst op dan interventie op een determinant met een grote invloed op een betrekkelijk zeldzame ziekte. Het roken van sigaretten blijkt het grootste gezondheidsverlies te bewerkstelligen: de prevalentie van roken is in Nederland hoog (40% van de mannen en vrouwen van 20-59 jaar). Het roken van sigaretten beinvloedt de mortaliteit van een aantal indicatoren (longkanker, keelkanker, slokdarmkanker, coronaire hartziekten, beroerte, en CARA). Coronaire hartziekten heeft het grootste aantal determinanten waarvoor PAR's konden worden berekend. De algemene conclusie is dat er voor genoemde gezondheidsproblemen in Nederland, althans theoretisch, nog een aanzienlijke gezondheidswinst is te boeken. Aangezie, In this report population-attributable risks (PARs) are reported, which quantify the contribution of several determinants (lifestyle factors such as smoking, alcohol consumption, physical activity and dietary factors, as well as biological risk factors such as total serum cholesterol, HDL-cholesterol, blood pressure, glucose tolerance and body mass index) to mortality from a number of chronic diseases (coronary heart disease, stroke, COPD, diabetes and some forms of cancer). Relative risks and prevalences of risk factors are needed for calculations of PAR's. Relative risks were taken from the international literature and risk factor prevalences (mainly for the age range 20-59 years) were derived from the 1987-1991 Dutch Monitoring Project on Cardiovascular Disease Risk Factors. Some important assumptions and difficulties in calculating and interpreting the PAR's and PAR like measures are summarized in chapter 2. Chapter 3 contains a description of PAR calculations for a series of determinants, later summarized (chapter 4) from the viewpoints of both diseases and determinants. PAR's for individual determinants ranged from 10 to 90 percent. From a Public Health point of view, intervention in a determinant which has a moderately strong influence one or more frequently occurring diseases, will lead to more gain in health than intervention in a determinant which has a strong influence on a rare disease. From the results it is clear, that cigarette smoking is the determinant causing the greatest health loss: the prevalence of cigarette smoking is still high (about 40 percent in men and women aged 20-59 years) in the Netherlands. Cigarette smoking influences mortality from a number of indicators (cancer of the lung, larynx, oral cavity and oesophagus, coronary heart disease, stroke and chronic respiratory disorders). Coronary heart disease has the largest number of determinants for which it was possible to calculate PARs. The general conclusion is that for the health probl

RIVM rapport:Tot voor kort was bij diegenen die aan kanker overleden maagkanker de belangrijkste doodsoorzaak, echter sinds de tweede wereldoorlog dalen in de gehele wereld de sterfte cijfers voor maagkanker. Er worden twee typen maagkanker onderscheiden, het diffuse en het intestinale type. Het ontstaan van beide typen loopt waarschijnlijk langs verschillende wegen. Er wordt verondersteld dat het diffuse type meer met aangeboren erfelijke factoren samenhangt, terwijl het intestinale type eerder beinvloed lijkt te worden door omgevingsfactoren. Enkele belangrijke risicofactoren voor (voorstadia van) maagkanker zijn een infectie met Helicobacter pylori, het eten van veel zout en koolhydraten, het weinig eten van groenten en fruit, en blootstelling aan N-nitroso verbindingen. Het relatieve belang van deze factoren verschilt waarschijnlijk tussen verschillende bevolkingen. In voedingsmiddelen en in de maag kunnen N-nitroso verbindingen worden gevormd uit nitriet en nitroseerbare stoffen door zuur-gekatalyseerde nitrosering en door bacterie-gekatalyseerde nitrosering. Ascorbinezuur, tocopherolen, en (poly)fenolen zijn naast anti-oxidanten ook remmers van de nitroseringsreactie door in een zure omgeving als substraat te dienen voor nitroserende stoffen. Ascorbinezuur kan zowel bij een lage pH de zuur-gekatalyseerde nitrosering remmen alswel de bacterie-gekatalyseerde nitrosering die bij neutrale pH plaatsvindt. Het veel eten van groenten en fruit - belangrijke leveranciers van ascorbinezuur en andere potentiele remmers van maagkanker zoals beta-caroteen - werkt waarschijnlijk beschermend zowel vroeg als laat in het ontstaansproces van maagkanker en kan daarom worden aanbevolen. Er is nog veel onderzoek nodig naar de rol van N-nitroso verbindingen bij het ontstaan van maagkanker. Kortom, er bestaat een grote behoefte aan testen die de endogene vorming van specifieke N-nitroso verbindingen in de maag nauwkeurig kunnen weergeven., Until recently, gastric cancer was the leading cause of cancer mortality, but since the Second World War mortality rates have started to decline world-wide. Two types of gastric cancer have been identified, the diffuse type and the intestinal type, and they seem to be caused via different pathways. Diffuse gastric cancer is supposed to be more related to genetic susceptibility, while intestinal gastric cancer (the focus of this thesis) is supposed to be largely influenced by environmental factors. Some important risk factors that have been related to GC and its precursor lesions are the infection with H. pylori, a high salt and carbohydrate intake, a low intake of vegetables and fruit, and exposure to NOCs. The relative importance of these factors is likely to vary between populations. NOCs can be formed exogenously in foods and endogenously in the stomach from nitrite and nitrosatable compounds, through acid-catalysed nitrosation (ACN) and through bacteria-catalysed nitrosation (BCN). Inhibitors of the nitrosation reaction are ascorbic acid, tocopherols, and (poly)phenols, that apart from being potent antioxidants, also work as a substrate for nitrosating species under acidic conditions. Ascorbic acid can inhibit both ACN at low pH values and BCN at neutral pH values. A high intake of fruits and vegetables, important sources not only of ascorbic acid but also of other potential gastric carcinogenesis inhibitors such as beta-carotene, is likely to be protective and therefore recommendable in the early as well as the later stages of gastric carcinogenesis. Much research remains to be done to clarify the role of NOCs in gastric carcinogenesis. If NOCs play a role in the aetiology of gastric cancer, their composition most likely differs between countries. Thus, there is a special need for tests that can accurately assess endogenous formation of specific NOCs in the human stomach.

RIVM rapport:The aim of the MORGEN-project is monitoring of risk factors for chronic diseases in the general population (cardiovascular disease, cancer, respiratory diseases, diabetes mellitus, low back pain, neck and shoulder complaints and migraine). Each year a new random sample of approximately 5000 subjects will be examined between 1993 and 1997. Data collection includes self-administerated questionnaires, medical examination, determination of cholesterol and random glucose levels in blood. Part of the blood is stored at -196 degrees C for future analyses. Data from the MORGEN-project will make an important contribution to policy-oriented public health research.

RIVM rapport:Het project Monitoring Risicofactoren en Gezondheid in Nederland (het "MORGEN-project") is een onderzoeksproject van het Rijksinstituut voor Volksgezondheid en Milieuhygiene (RIVM), waarin de gezondheidssituatie en het voorkomen van risicofactoren wordt gemeten in een steekproef van de Nederlandse bevolking gedurende de periode 1993 tot en met 1997. In 1993 werden 5154 mannen en vrouwen onderzocht. De prevalentiecijfers van de meest relevante risicofactoren (verhoogd cholesterolgehalte, hypertensie, obesitas) waren vergelijkbaar met die van het Peilstationsproject 1987-1991. Het percentage sigarettenrokers was ten opzichte van de periode 1987-1991 gedaald van 40% naar 37%. De zelf-gerapporteerde prevalentie van astma was 3%. Bijna de helft van degenen met astma gebruikte daarvoor regelmatig medicijnen. Lage rugpijn en nek- en schouderklachten in de 12 maanden voorafgaand aan het onderzoek werd door bijna de helft van de deelnemers gerapporteerd. Ruim 10% had weleens 1 week of langer van het werk verzuimd ten gevolge van de klachten. Ongeveer 9% van de onderzoekspopulatie rapporteerde regelmatige hoofdpijn met verschijnselen van migraine. De prevalentie van zelf-gerapporteerde diabetes was ongeveer 1%. Op basis van hoge niet-nuchtere glucose waarden werd diabetes geconstateerd bij 0.8% van de mannen en 0.1% van de vrouwen die geen diabetes hadden gerapporteerd., The Monitoring Project on Risk Factors for Chronic Diseases (MORGEN-project) is conducted by the National Institute of Public Health and Environmental Protection (RIVM). Its general purpose is to determine the prevalence of risk factors for chronic diseases as well as the prevalence of some specific chronic conditions in a sample of the general population. In the MORGEN-project, data on the health status and prevalence of risk factors are collected in a random sample of the general population in the Netherlands from 1993 through 1997. In 1993, 5154 men and women participated in the MORGEN-project. The prevalence figures of the most relevant risk factors (hypercholesterolemia, hypertension, obesity) are comparable to those observed in the Monitoring Project on Cardiovascular Disease Risk Factors 1987-1991. The proportion of smokers however, decreased from 40% over the period 1987-1991 to 37% in 1993. The prevalence of self-reported asthma was 3%. Almost half of those with asthma reported regular use of medication. The prevalence of low back pain and of neck-shoulder complaints was approximately 50%. Of those with low back pain or neck and shoulder complaints, 10% had been on sick leave for longer than one week due to their complaints. Approximately 9% of the respondents reported regular headache with symptoms of mi74aine. The prevalence of self-reported diabetes was about 1%. Based on non-fasting glucose measurements, diabetes was diagnosed in an additional 0.8% of men and 0.1% of women.

RIVM rapport:The aim of this project is to study trends in the major risk factors for cardiovascular diseases e.g. total and HDL chlolesterol, blood pressure and smoking. Also the importance of less frequently measured risk factors e.g. contraceptive pill use and psycho-social factors in the etiology of cardiovascular diseases will be investigated. Pilot investigations were carried out in order to investigate the possibilities to extend the project towards a monitoring project on (risk factors for) chronic diseases. These projects were carried out in Amsterdam, Doetinchem and Maastricht. In the sixth year (1992) of this project a total of about 6,000 persons, aged 20-59, were examined.

RIVM rapport:The aim of this project is to study trends in the major risk factors for cardiovascular diseases e.g. total and HDL cholesterol, blood pressure and smoking. Also the importance of less frequently measured risk factors e.g. contraceptive pill use and psycho-social factors in the etiology of cardiovascular diseases will be investigated. Biologic material e.g. whole blood, plasma, white and red cells will be kept frozen at - 20 degrees C for future etiologic studies. This project is carried out in Amsterdam, Doetinchem and Maastricht. In the fifth year (1991) of this project a total of 7,500 persons, aged 20-59, were examined.

RIVM rapport:The relation between gallstone size and gallbladder cancer was studied in a hospital based case-control study. Cases were selected on abdominal surgery. The selection criterion for controls was a cholecystectomy performed for a benign gallbladder disorder. Controls were matched with cases on sex, age, hospital and date of admission. A radiologist determined the size of the largest gallstone within the gallbladder by reviewing hard copies of sonographical examinations. Between 1983 and 1989 83 gallbladder cases were identified in the 18 participating hospitals. Of 43 cases and 98 matched controls a measurable stone size was obtained. No relation was found between size of the largest stone within the gallbladder and the occurrence of gallbladder cancer.

RIVM rapport:We studied the relation between diet and biliary tract cancer in a case-control study, comprising 111 incident cases and 480 controls from the general population. Food intake was assessed with a semi- quantitative food frequency questionnaire, which covered diet comprehensively. In half of the cases and 30% of the controls the information was obtained from the spouse or other relatives (indirect respondents). Mono- and disaccharides showed an elevated risk, independent from other sources of energy. Vegetables and beta-carotene showed a reduced risk. Associations were stronger among the indirect respondents. Findings on mono-disaccharides were discussed in connection with bloodlipids, bile composition and gallstone formation.

RIVM rapport:Ten behoeve van het internationale patient-controle onderzoek naar de relatie tussen voeding en kanker van pancreas, galblaas en galwegen in het kader van het SEARCH-project (IARC, Lyon) is de gebruikelijke opname van voedingsmiddelen gemeten met behulp van een semikwantitatieve voedselfrequentie vragenlijst. Aangezien voedingsmiddelen en eetgewoonten in de deelnemende landen niet vergelijkbaar zijn, is besloten dat ieder deelnemend onderzoekscentrum alleen schattingen van de opname van voedingsstoffen rapporteert. Teneinde dit te realiseren is het noodzakelijk de nutrientensamenstelling van de voedingsmiddelen te weten. er moest een voedingsmiddelentabel worden opgesteld, hierna te noemen SEARCH tabel, met daarin opgenomen nutrienten die voor het onderzoek van belang werden geacht. De uiteindelijke SEARCH tabel heeft als basis de UCV tabel 1985. De afdeling Voeding van het TNO-CIVO heeft de SEARCH tabel in opdracht van het RIVM aangevuld met analyses van in de UCV ontbrekende vitamines en mineralen, van aminozuren, van vetzuren en met de nutrienten van enkele samengestelde voedingsmiddelen.