Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. METHODS: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. RESULTS: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. CONCLUSION: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.

Occupation and risk of glioma, meningioma and acoustic neuroma: results from a German case-control study (interphone study group, Germany).

BACKGROUND: Several epidemiological studies have investigated the association between occupation and brain tumour risk, but results have been inconclusive. We investigated the association between six occupational categories defined a priori: chemical, metal, agricultural, construction, electrical/electronic and transport, and the risk of glioma, meningioma and acoustic neuroma. METHODS: In a population-based case-control study involving a total of 844 cases and 1688 controls conducted from 2000 to 2003, detailed information on life-long job histories was collected during personal interviews and used to create job calendars for each participant. Job title, job activity, job number, and the starting and ending dates of the activity were recorded for all activities with duration of at least 1 year. Reported occupational activities were coded according to the International Standard Classification of Occupations 1988 (ISCO 88). For the analyses we focused on six a priori defined occupational sectors, namely chemical, metal, agricultural, construction, electrical/electronic and transport. Multiple conditional logistic regression analysis was used to estimate odds ratios and their 95% confidence intervals. RESULTS: Most of the observed odds ratios were close to 1.0 for ever having worked in the six occupational sectors and risk of glioma, meningioma and acoustic neuroma. Sub-group analyses according to duration of employment resulted in two elevated odds ratios with confidence intervals excluding unity. CONCLUSIONS: We did not observe an increased risk of glioma or meningioma for occupations in the agricultural, construction, transport, chemical, electrical/electronic and metal sectors. The number of 'significant' odds ratios is consistent with an overall 'null-effect'.

Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany).

The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study in Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multiple logistic regression models. Increased risks were found for exposure to persistent noise (OR=2.31; 95% CI 1.15-4.66), and for hay fever (OR=2.20; 95% CI 1.09-4.45), but not for ionising radiation (OR=0.91; 95 % CI 0.51-1.61) or regular mobile phone use (OR=0.67; 95% CI 0.38-1.19). The study confirms results of recently published studies, although the pathogenetic mechanisms are still unknown.

Case-control study of lifetime occupational and recreational physical activity and risks of colon and rectal cancer.

Important aspects of the inverse relation between physical activity and colon cancer risk are still under discussion. In 2000-2003, 239 incident cases of colorectal cancer confirmed by histopathology and 239 hospital-based controls, matched by age and gender, were enrolled. In standardized interviews, data on occupational and recreational physical activity for ages 20, 30, 40, 50 and 60 years were collected from 98 colon cancer cases, 141 rectal cancer cases, and from 193 controls. Besides lifestyle and sociodemographic characteristics, a detailed food frequency questionnaire was assessed. In multivariate logistic regression for colon cancer, significant risk reductions for the highest quartile of total physical activity were found for almost all ages. For lifetime mean physical activity, the multivariate odds ratio for the highest quartile was 0.37 [95% confidence interval (CI) 0.17, 0.83]. For lifelong constantly high-exercisers compared with lifelong non-exercisers an odds ratio of 0.26 (95% CI 0.08, 0.84) was estimated. For rectal cancer, no consistent association with physical activity was found. No confounding effects were observed but the authors found effect modification with total energy intake. These data support an inverse association of colon cancer risk and physical activity which is most expressed if activity is kept up throughout life.

European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection.

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

The contribution of cigarette smoking to bladder cancer in women (pooled European data).

BACKGROUND: Using a combined analysis of 11 case-control studies from Europe, we have investigated the relationship between cigarette smoking and bladder cancer in women. METHODS: Available smoking information on 685 female bladder cancer cases and 2416 female controls included duration of smoking habit, number of cigarettes smoked per day, and time since cessation of smoking habit for ex-smokers. RESULTS: There was an increasing risk of bladder cancer with increasing duration of smoking, ranging from approximately a two-fold increased risk for a duration of less than 10 years (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.1) to over a four-fold increased risk for a duration of greater than 40 years (OR = 4.1, 95% CI 3.0-5.5). A dose-response relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 3.8 (95% CI 2.7-5.4), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% in the immediate 1-4 years after cessation, OR = 0.68 (95% CI 0.38-1.2). However, even after 25 years the decrease in risk did not reach the level of the never-smokers, OR = 0.27 (95% CI 0.21-0.35). CONCLUSION: The proportion of bladder cancer cases among women attributable to ever smoking was 0.30, (0.25-0.35) and to current smoking was 0.18 (0.14-0.22). These attributable proportions are less than those observed among men, although they are likely to increase in the future as the smoking-related disease epidemic among women matures.

Cigar, pipe, and cigarette smoking and bladder cancer risk in European men.

OBJECTIVE: Estimating the risk of bladder cancer from cigar and pipe smoking is complicated by a small number of non-cigarette smokers included in most relevant studies. METHODS: We undertook a pooled analysis of the data on men from six published case-control studies from Denmark, France, Germany, and Spain, to assess the association between pipe and cigar smoking and bladder cancer, and to compare it with the risk from cigarette smoking. Complete history of tobacco smoking was ascertained separately for cigarettes, cigars, and pipe. Odds ratios (ORs) were estimated after adjusting for age, study, and employment in high-risk occupations. RESULTS: The pooled data set comprised 2279 cases and 5268 controls, of whom 88 cases and 253 controls smoked only cigars or pipe. The OR for pure cigarette smoking was 3.5 (95% confidence interval [CI] 2.9-4.2), that for pure pipe smoking was 1.9 (95% CI 1.2-3.1) and that for pure cigar smoking was 2.3 (95% CI 1.6-3.5). The increase in the OR of bladder cancer that was observed with duration of smoking was non-significantly lower for cigars than for cigarettes. CONCLUSION: Our results suggest that smoking of cigars and pipe is carcinogenic to the urinary bladder, although the potency might be lower than for cigarettes.

Nutrient intake patterns in gastric and colorectal cancers.

The purpose of the study was to present the dietary risk pattern in gastric and colorectal cancers, using the same methodological approach in a parallel hospital-based case-control study. In all, 180 cases of colorectal cancer and 80 cases of stomach cancer, confirmed histopathologically, were enrolled from the University Hospital in Cracow. A high intake of carbohydrates was associated with an increased risk of colorectal cancer (OR = 2.45). For stomach cancer, a moderate consumption of carbohydrates markedly increased relative risk (OR = 4.29), while a high intake of carbohydrates increased the risk by 8.73. The patterns of dietary risk factors related to intake of fats were definitively different in both cancer sites. The higher fat consumption was not associated with the higher risk of stomach cancer. A medium intake of fats increased the risk of colorectal cancer by 1.96 and that above 83 g/day by 2.20. In colorectal cancer, the significant protective effect of retinol, carotene and vitamin C has been evidenced, however, only carotene and vitamin E were inversely correlated with stomach cancer.

Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case-control study in Poland.

The purpose of the study was to assess the relation between the simultaneous exposure to alcohol and consumption of micronutrients that have protective properties against colorectal cancer. A hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 at the University Hospital in Krakow, Poland. In total, 180 incident cases of colorectal cancer, confirmed by histopathology, were recruited and an equal number of controls, individually matched by gender and age (+/-5 y), were chosen amongst patients with no history of cancer. A food-frequency questionnaire for 148 food items, combined with the quantity of foods eaten, was used to assess the normal dietary pattern. The data confirmed the reported inverse association between the intake of retinol, thiamine, or antioxidant micronutrients (vitamins C, E) and the occurrence of colorectal cancer. Alcohol intake was found to be an important risk factor for this cancer site, and the risk escalated in parallel with increased intake of retinol, carotene, vitamins C and E, but with high consumption of alcohol ran a noticeably high risk of colorectal cancer (OR= 6.79; 95% CI: 2.08-22.18). The risk was markedly lower, however, among alcohol drinkers who reported a high intake of micronutrients (OR = 1.35; 95% CI: 0.39-4.67). The data suggest that a combination of high consumption of alcohol and low intake of retinol and antioxidant vitamins may considerably increase the risk of colorectal cancer.

Combined risk assessment of physical activity and dietary habits on the development of colorectal cancer. A hospital-based case-control study in Poland.

The purpose of the study was to assess the importance of physical activity performed both in occupational settings and in leisure time on the risk of colorectal cancer, considering the possible confounding effects of dietary habits. The hospital-based case-control study was carried out in Poland. In total, 180 incident cases of colorectal cancer were recruited. An equal number of controls, individually matched by gender and age, were chosen from patients with no history of cancer. A food frequency questionnaire combined with quantity of foods eaten was used to assess the usual dietary pattern for 148 food items. The average physical load of the interviewed patients before the occurrence of disease was ascertained by self-assessment. The degree to which patients' recreational time was sedentary was measured by the number of hours spent watching TV. The adjusted risk of colorectal cancer was reduced by half in those active in leisure time (OR 0.45, 95% CI 0.24-0.84). The effect of occupational physical activity was of about the same order of magnitude in terms of risk reduction (OR 0.61, 95% CI 0.29-1.29) and both activities combined acted as independent protective factors. The protective effect of healthy nutrition appeared to be independent from that attributed to physical effort.

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies.

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48-2.61) to 5.57 after 60 years (CI 4.18-7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 4.50 (CI 3.81-5. 33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1-4 years, OR = 0.65 (0. 53-0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0. 30-0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17-0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61-0.70) for all men and 0.73 (0.66-0.79) for men younger than 60. These estimates are higher than previously calculated.

Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries.

BACKGROUND: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case-control studies. METHODS: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. RESULTS: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8-1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0-3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. CONCLUSION: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.

EPIC-Germany--A source for studies into diet and risk of chronic diseases. European Investigation into Cancer and Nutrition.

The 'European Investigation into Cancer and Nutrition (EPIC)' represents one of the main scientific activities of the EU program 'Europe against Cancer' and is a large-scale cohort study on diet and chronic diseases, especially cancer, with approximately 475,000 study participants. The German contribution amounted to 53,000 study participants recruited between 1994 and 1998. The study instruments of the baseline examination included self-administered questionnaires for optical reading, PC-guided interviews, and physical examinations. These instruments covered different aspects of lifestyle, with a particular focus on diet. In addition, about 95% of the participants provided 30 ml of blood. The blood was stored in liquid nitrogen for further use, preferentially in nested case-control studies. All interviews and examinations were conducted by trained interviewers in examination centers established for this study in local health offices. Every 2 years, a follow-up questionnaire is mailed to the study participants. The follow-up questionnaires will be used as the major source of outcome information and to update exposure information. The self-reported diseases are verified by medical data. In the future, record linkage with local cancer registries will help to support the identification and collection of incident cancer cases. Only an outline of hypotheses was formulated at the very beginning of EPIC in 1992. In the future, each etiological study will be based on detailed research hypotheses according to the existing knowledge and identified research gaps. These studies will be conducted on cancer at the international level and on non-cancer diseases at the national or local level.

Quantitative food intake in the EPIC-Germany cohorts. European Investigation into Cancer and Nutrition.

The EPIC-Heidelberg and the EPIC-Potsdam studies with about 53,000 study participants represent the German contribution to the EPIC (European Investigation into Cancer and Nutrition) cohort study. Within the EPIC study, standardized 24-hour dietary recalls were applied as a quantitative calibration method in order to estimate the amount of scaling bias introduced by the varying center-specific dietary assessment methods. This article presents intake of food items and food groups in the two German cohorts estimated by 24-hour quantitative dietary recalls. Recalls from 1,013 men and 1,078 women in Heidelberg and 1,032 men and 898 women in Potsdam were included in the analysis. The intake of recorded food items or recipe ingredients as well as fat used for cooking was summarized into 16 main food groups and a variety of different subgroups stratified by sex and weighted for the day of the week and age. In more than 90% of the recalls, consumption of dairy products, cereals and cereal products, bread, fat, and non-alcoholic beverages, particularly coffee/tea, was reported. Inter-cohort evaluations revealed that bread, potatoes, fruit and fat were consumed in higher amounts in the Potsdam cohort while the opposite was found for pasta/rice, non-alcoholic, and alcoholic beverages. It was concluded that the exposure variation was increased by having two instead of one EPIC study centers in Germany.

Occupation and bladder cancer in European women.

OBJECTIVES: We examined the importance of occupational exposures for bladder cancer in women. METHODS: We combined data from 11 case-control studies conducted between 1976 and 1996 in six European countries. The pooled data comprised 700 incident female cases and 2425 population or hospital controls, aged 30-79 years. Lifetime occupational and smoking history were examined using common coding. RESULTS: Excess risks were found in only a few of the occupations previously identified at high risk for bladder cancer. Statistically significant excess risks were observed for metal workers, particularly blacksmiths, toolmakers and machine tool operators (OR: 2.0, 95% CI: 1.1-3.6), tobacco workers (OR: 3.1, 95% CI: 1.1-9.3), field crop and vegetable farm workers (OR: 1.8, 95% CI: 1.0-3.1), tailors and dress makers (OR: 1.4, 95% CI: 1.0-2.1), saleswomen (OR: 2.6, 95% CI: 1.0-6.9), and mail sorting clerks (OR: 4.4, 95% CI: 1.0-19.5). About 8% (95% CI: 3.1 19.9) of all bladder cancers in women could be attributed to occupation after adjusting for smoking. The attributable risk was higher in women aged less than 65 years (12%), compared to older women (4%). CONCLUSIONS: The calculation of the attributable risk on the basis of results from this analysis may have caused some overestimation of the proportion of occupational bladder cancer in women. A significant proportion, however, of bladder cancer cases among European women less than 65 years is likely to be attributed to occupation. This link between bladder cancer in women and occupational factors has received little recognition, probably because studies addressing these issues have predominantly been done in men.

Role of medical history in brain tumour development. Results from the international adult brain tumour study.

In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40-12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49-0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61-0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.

Smoking as a confounder in case-control studies of occupational bladder cancer in women.

BACKGROUND: In studies in men, risk estimates on occupation and bladder cancer are distorted by about 10% when not adjusting for smoking. We examined the degree to which occupational risk estimates for bladder cancer in women are confounded by smoking, and the degree of residual confounding by inadequate control of this effect. METHODS: Primary data of 11 case-control studies on occupation and bladder cancer from Denmark, France, Germany, Greece, Italy, and Spain were pooled. Information for smoking and lifetime occupational history for 700 female cases and 2,425 female controls ages 30-79 was abstracted and recoded. Logistic regression was used to calculate odds ratios (OR) by occupation, applying five models which differed in their degree of adjustment for smoking. RESULTS: In major occupational groups, risk estimates were distorted by less than 10% when not adjusting for smoking. A statistically significant excess risk for bladder cancer was found in 13 specific occupations and industries. In most occupations, adjustment for smoking led the ORs towards the null value, but all statistically significant associations were maintained after adjustment. In three occupations (lathe operators, field crop workers, and wood manufacturers), a statistically significant excess risk was masked when not adjusting for smoking. In six occupations, estimates were distorted by more than 10% (-22% up to +40%). In occupations where smoking acted as a positive confounder, the proportion of confounding removed using a dichotomous smoking variable (ever/never) was around 60%. In one occupation (buyers), controlling for smoking status (ever, never) led to over-adjustment, because the percentage of smokers was high but the quantity smoked was low.