OBJECTIVE: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. METHODS: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977-1993; Sweden 1965-1993) were linked to tumor registry data for up to 15-28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. RESULTS: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5. 95% CI = 1.3-1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.62.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2-17.4), colon (SIR = 2.6, 95% CI = 1.6-3.8), and rectum (SIR = 2.5, 95% CI= 1.3-4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI= 1.2-5.0). thyroid (SIR = 3.7, 95% CI = 1.8-10.9), kidney (SIR = 3.2, 95% CI = 1.6-5.5), and bone (SIR= 13.8, 95% CI= 1.7-50.0). CONCLUSIONS: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-I system in the etiology of various cancers.
The hypothesis that exposure to traffic-related air pollution increases the risk of developing cancer during childhood was investigated. The authors enrolled 1,989 children reported to the Danish Cancer Registry with a diagnosis of leukemia, tumor of the central nervous system, or malignant lymphoma during 1968-1991 and 5,506 control children selected at random from the entire childhood population. The residential histories of the children were traced from 9 months before birth until the time of diagnosis of the cases and a similar period for the controls. For each of the 18,440 identified addresses, information on traffic and the configuration of streets and buildings was collected. Average concentrations of benzene and nitrogen dioxide (indicators of traffic-related air pollution) were calculated for the relevant period, and exposures to air pollution during pregnancy and during childhood were calculated separately. The risks of leukemia, central nervous system tumors, and all selected cancers combined were not linked to exposure to benzene or nitrogen dioxide during either period. The risk of lymphomas increased by 25% (p for trend = 0.06) and 51% (p for trend = 0.05) for a doubling of the concentration of benzene and nitrogen dioxide, respectively, during the pregnancy. The association was restricted to Hodgkin's disease.
The aims of the study were to evaluate if the front-door concentrations of benzene, toluene, and xylenes can be used to classify the personal exposures of Danish children and to identify factors that affect their personal exposure. Average concentrations were measured over 1 week with diffusive samplers, and the personal exposures of 98 children and the concentrations outside the front doors of their homes were measured simultaneously. Time and activity patterns were noted in diaries. The front-door concentrations were significantly higher in Copenhagen than in rural areas (all P
The aim of the study was to evaluate the predictions derived from the Danish Operational Street Pollution Model (OSPM) when the input data are obtained by simple methods that could be used in large-scale epidemiological studies. The model calculations were thus compared with passive sampler measurements of nitrogen dioxide and benzene at 103 street locations in Copenhagen, Denmark, and at 101 locations in rural areas. Data on traffic and street configuration were collected by means of a simple registration scheme in which forms were filled out by local municipal authorities. Meteorological data were derived from routine measurements at Copenhagen airport, and data on background air pollution were based on a simple empirical model. Differences in air pollution levels between rural areas and Copenhagen and differences in nitrogen dioxide concentrations at various locations in Copenhagen were well reproduced by the OSPM. The correlation coefficients (r) between the measured and the predicted half-year average concentrations of nitrogen dioxide in Copenhagen were between 0.75 and 0.80 for various degrees of precision of the input data for the model. The results indicate that the OSPM used with the presented methods for generation of input data might be useful in assessing long-term exposure to air pollutants in epidemiological studies.
BACKGROUND: A recent observational study suggested that the use of angiotensin-converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark. METHODS: Using data from the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17,897 individuals prescribed ACE inhibitors was compared with expected incidence based on county specific cancer rates during an 8-year study period with a mean follow-up of 3.7 years. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. In addition, the authors performed a direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers (n = 47,579 individuals) by means of a Cox proportional hazards model. RESULTS: Overall, 909 cancer cases were observed among users of ACE inhibitors, with 846 expected based on general population rates, yielding an SIR of 1.07 (95% CI, 1.01-1.15). No risk reductions were observed for cancers of the breast and female reproductive tract, whereas nonsignificantly decreased SIRs were observed for cancers of the esophagus, stomach, and liver. Cancer of the kidney was found in significant excess (SIR, 1.6; 95% CI, 1.1-2.2). Stratification by duration of follow-up or number of prescriptions revealed no apparent trends, except for a tendency toward decreasing risk with increasing length of follow-up for smoking-related cancers. The direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers yielded results comparable to those derived from the comparison with the general population, with a hazard ratio for cancer overall of 1.01 (95% CI, 0.93-1.09). CONCLUSIONS: This large, population-based cohort study did not confirm a protective effect of ACE inhibitors on the development of cancer. The excess of kidney cancer observed likely reflects a correlation between hypertension and kidney cancer. Further investigation is needed to evaluate the long-term effects of ACE inhibitors beyond the observation period of this and previous studies. Also, the suggestive evidence of decreased risks for upper digestive system cancers and for smoking-related cancers over time may warrant additional investigation.
OBJECTIVE: Energy restriction reduces the incidence of malignant tumors in experimental animals, but evidence for a similar effect in humans is lacking. To test the hypothesis in humans, we investigated cancer incidence among patients with anorexia nervosa, who have had an extremely low intake of calories for prolonged periods of their lives. METHODS: Patients with anorexia nervosa (2151 women and 186 men) during 1970-1993 were identified in the population-based Danish Psychiatric Case Register and the National Registry of Patients. The cohort was linked to the Danish Cancer Registry, and cancer incidence among cohort members was compared with that of the general population. RESULTS: The overall cancer incidence among women with anorexia nervosa was reduced by a factor of 0.80 (95% confidence interval 0.52-1.18) below that of the general population on the basis of 25 observed and 31.4 expected cases. Among men, two cases of cancer were observed, both confined to the brain, whereas 0.2 cases were expected. CONCLUSIONS: The finding of a slight reduction in cancer risk among women with anorexia nervosa may support the theory that a low-energy diet may decrease tumor development in humans. However, longer follow-up and control for confounding factors are needed to obtain more convincing evidence.
Antidepressants appear to promote tumor growth in experimental studies; however, results from epidemiologic studies are inconclusive. We used a population-based cohort study to estimate the incidence of cancer after antidepressant treatment in 39,807 adult users of antidepressants identified in the Prescription Database of the County of North Jutland, Denmark between January 1, 1989 and December 31, 1995. Information on cancer occurrence was obtained from the Danish Cancer Registry. We categorized exposure according to use of tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, or monoamine oxidase inhibitors. In the follow-up period beginning 1 year after first known prescription, there were 966 cancers among users of antidepressants; our population estimate suggested an expected number of 946 for an overall standardized incidence ratio of 1.0 (95% confidence interval = 1.0-1.1). Users of tricyclic antidepressants had an excess of non-Hodgkin's lymphoma, with the risk increasing with the number of prescriptions of tricyclic antidepressants. The standardized incidence ratio was 2.5 (95% confidence interval, 1.4-4.2) for those with five or more prescriptions. Our results provide little evidence that antidepressants promote cancer at other sites, except for a possible effect of tricyclic antidepressants and tetracyclic antidepressants on non-Hodgkin's lymphoma.
The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymphoma and for 94% of 171 cancer-free control patients. Use of anticonvulsive drugs was correlated with angiographic procedures that used Thorotrast, a well-known human liver carcinogen. After exclusion of study subjects exposed to Thorotrast, no association was seen between treatment with phenobarbital and cancer of the liver (odds ratio, 1.0; 95% confidence interval, 0.1-8.0) or biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1-4.2). Furthermore, a histopathological evaluation of slides from 7 of 9 liver cancer patients not treated with Thorotrast revealed that 3 of the 4 cases of hepatocellular carcinoma involved cirrhosis of the liver, which suggested an etiological role for alcohol or viral hepatitis. A possible link was observed between use of phenytoin and risk for non-Hodgkin's lymphoma (1.8; 0.5-6.6), with a rising trend in risk with increasing dose. Our results suggest that the increased risk for cancers of the liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrhosis of the liver rather than to anticonvulsive treatment.