Jürgen Wahrendorf

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. Int. J. Cancer82:155–160, 1999.

EPIC-Germany – A Source for Studies into Diet and Risk of Chronic Diseases

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.

Occupation and bladder cancer among men in Western Europe

Objectives: We examined which occupations and industries are currently at high risk for bladder cancer in men. Methods: We combined data from 11 case–control studies conducted between 1976–1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30–79 years. Lifetime occupational and smoking histories were examined using common coding. Results: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02–1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07–1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. Conclusions: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.

International renal cell cancer study. VII. role of diet

We investigated the role of diet in the etiology of renal cell cancer (RCC) in a multi‐center, population‐based case‐control study conducted in Australia, Denmark, Sweden and the United States, using a shared protocol. A total of 1,185 incident histopathologically confirmed cases (698 men, 487 women) and 1,526 controls (915 men, 611 women) frequency‐matched to cases by sex and age were included in the analyses. The association between RCC and diet was estimated by relative risks (RR) and 95% confidence intervals (CI) adjusted for age, sex, study center, body mass index and smoking. A statistically significant positive association was observed for total energy intake (RR = 1.7, 95% CI = 1.4–2.2 for the highest vs. lowest quartile, p value for trend <0.00001), while the hypothesis that protein and fat are risk factors independent of energy was not supported. Fried meats were associated with increased RCC risk, while vegetables and fruits were protective, with the strongest effect observed for the highest quartile of consumption of orange/dark green vegetables but not vitamin C or β carotene. Increased risk was associated with low intake (lowest decile) of vitamin E and magnesium. We observed an apparent protective effect of alcohol confined to women and probably due to chance. Our findings indicate an important role of nutrition in the development of RCC. The apparent positive association of energy intake with risk of RCC needs further investigation in a prospective cohort study to exclude the possible impact of differences in recall between cases and controls.

A case-control study of lung cancer with special reference to the effect of air pollution in Poland.

STUDY OBJECTIVE--The aim of the study was to assess the affect of inhaled pollutants on lung cancer risk. DESIGN--The study was a retrospective case-control survey of lung cancer deaths over a six year period (1980-1985). Information on occupation, smoking habits, and residency was collected from next of kin. Classification of exposure to community air pollution was based on measured levels of total suspended particular matter and sulphur dioxide. SETTING--Cases and controls had been resident in the city of Cracow, Poland. PARTICIPANTS--Cases were male (n = 901, questionnaire response rate 70.7%) and female (n = 198, response rate 65.1%) lung cancer deaths; controls were deaths from other causes, excluding other respiratory diseases, and frequency matched by age and sex (males n = 875, response rate 73.5%; females n = 198, response rate 64.0%). MAIN RESULTS--Lung cancer risk was found to depend strongly on total cigarette consumption, on age at starting to smoke, and on time since stopping smoking. Relative risk estimates for occupational exposure in iron and steel foundries or in other industries were significantly increased in males. Relative risk in men for highest air pollution level was 1.48 (95% confidence interval 1.08-2.01), while in women the increase was not significant. The joint action of the risk facts of smoking, occupational exposure, and air pollution was found to fit almost perfectly into a multiplicative model. CONCLUSIONS--Under conditions found in Cracow, air pollution may increase lung cancer risk, acting multiplicatively with known risk factors such as smoking and industrial exposure.

Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins

In an occupational cohort study, the relation between exposure to phenoxy herbicides, and contaminants (dioxins and furans) and cancer mortality was investigated. A total of 2,479 workers from four plants in Germany were included, with a mortality follow-up until the end of 1989 (for one cohort, until the end of 1992). A total of 484 deaths were recorded yielding a standardized mortality ratio (SMR) of 101 (95 percent confidence interval [CI]=92–111) for total mortality, and an SMR of 119 (CI=100–141) for all malignant diseases. A variety of herbicides was produced, including those which are known to have been contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). High dioxin and furan exposure (in particular, exposure to TCDD, but also to higher chlorinated dioxins) had occurred in two of the four plants as shown by blood-fat measurements in a sample of workers. Mortality from all neoplasms increased with latency and was highest in the largest plant where the highest TCDD blood levels were recorded. An increased mortality in the total cohort from respiratory cancer (SMR=154, CI=115–202), cancer of the buccal cavity and pharynx (SMR=295, CI=135–560), and non-Hodgkins lymphoma (SMR=326, CI=119–710) was observed. Our findings are consistent with results from other cohorts which showed an increased overall cancer mortality and mortality of respiratory cancer after long-term exposure to these phenoxy herbicides and dioxins.

Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case-control study in Poland.

A hospital-based, multicenter, case-control study has been performed in Poland covering 741 incident stomach-cancer cases (520 males and 221 females) and the same number of controls. All stomach-cancer diagnoses were evaluated for histologic type according to the Lauren criteria. Fifty-one percent were of the intestinal type, 35 percent of the diffuse type, and 8.5 percent of the mixed type. The frequency of consumption of individual food items and several food groups was analyzed and the association of various foods with stomach cancer risk was evaluated after controlling for sex, age, occupation, education, and residency. Increased consumption of sausages was related significantly to gastric cancer risk, whereas increased consumption of cheese products, nonwhite bread, vegetables, and fruit was associated with decreased risk. A particularly strong decrease in risk was associated with consumption of radishes and onions. When consumption of fruits and vegetables, sausages, nonwhite bread, and cheese were introduced simultaneously in a multivariate model, independent effects were found only for fruit and vegetables, sausages, and nonwhite bread. The use of table salt, the frequency of eating hot meals, and an irregular eating pattern were also associated with increased risk, while additional consumption of fruit between meals showed reduced risk. If a reduction in vegetable and fruit consumption took place after marriage, an increased risk for stomach cancer was found, whereas augmented consumption of these food items after marriage decreased the risk. Separate risk models were calculated for stomach cancer of the intestinal and diffuse types, but both histologic varieties showed the same pattern of associations with dietary risk factors.

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

AbstractBackground: 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.

International renal-cell-cancer study. VI. The role of medical and family history

A number of medical conditions have been linked with renal‐cell cancer, although the evidence is not consistent in every case. In a large international case‐control study of renal‐cell cancer, we examined, among other hypotheses, associations with a personal history of certain medical conditions and a family history of cancer of the kidney or thyroid. Relative risks (RR), adjusted for the effects of age, gender, body‐mass index, tobacco smoking and study centre, were significantly increased by a history of kidney stones or thyroid or kidney disease. The RR were not altered by additional adjustment for hypertension, or when diagnoses were restricted to those made at least 5 or 10 years before 1987 (the usual “cut‐off” date). The link with kidney injury is particularly likely to be affected by recall bias. Increased RR of borderline significance were found for kidney infection (RR, 1.2) and diabetes (RR, 1.4). Having one first‐degree relative with kidney cancer was associated with a significantly increased risk of renal‐cell cancer (RR, 1.6; 95% Cl, 1.1–2.4). Seven cases reported 2 first‐degree relatives with kidney cancer. No controls had first‐degree relatives with kidney cancer. None of our participants reported having von Hippel‐Lindau disease. The data suggests that a few conditions of the kidney are strongly associated with renal‐cell cancer and that heredity plays a role in a small proportion of cases.

Tobacco, alcohol, and diet in the etiology of laryngeal cancer: a population-based case-control study

Cancer of the larynx constitutes an increasingly important problem in Polish males during the last 25 years. A population-based case-control study of laryngeal cancer among people under 65 years of age was conducted in Lower Silesia, a province in Southwest Poland, from 1986 to 1987, with 249 newly-diagnosed cancer cases and 965 controls. The estimated relative risk (RR) for smoking and alcohol are both very high: for smoking more than 30 cigarettes, RR=59.7 (95 percent confidence interval [CI]: 13.0–274); for drinking vodka regularly for more than 30 years, RR=10.4 (95 percent CI: 4.0–27.2). Exposures to alcohol and tobacco show a clear multiplicative effect in all categories of exposure. The risk was shown to be reduced by quitting smoking (RR=0.3, 95 percent CI: 0.14–0.64, after 10 years) or by having a history of intermittent smoking. Poor nutrition was also identified as a strong independent risk factor. However, data quality regarding this factor is not as high as for tobacco and alcohol. Smoking alone accounts in this study for an estimated 95.2 percent of all the cases of laryngeal cancer.