BACKGROUND: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect METHODS: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics RESULTS: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated CONCLUSIONS: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.
Comment In: N Engl J Med. 2001 Dec 20;345(25):1844-611752364
Comment In: N Engl J Med. 2002 May 16;346(20):1588-9; author reply 1588-912015402
Comment In: N Engl J Med. 2002 May 16;346(20):1588-9; author reply 1588-912017163
The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965-83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4, 95 percent confidence interval [CI] = 1.3-1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3-1.6) and among women (SIR = 1.5, CI = 1.1-2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9-5.7), esophagus (SIR = 6.8, CI = 4.5-9.9), larynx (SIR = 3.3, CI = 1.7-6.0), and lung (SIR = 2.1, CI = 1.7-2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9-2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6-1.4), large bowel (SIR = 1.1, CI = 0.8-1.5), prostate (SIR = 1.0, CI = 0.8-1.3), urinary bladder (SIR = 1.0, CI = 0.6-1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3-1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6-2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5-9.1).(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to determine the risk of developing primary liver cancer in patients with a diagnosis of alcoholism, liver cirrhosis, or both. Three population-based, mutually exclusive cohorts were defined on the basis of hospital discharge diagnosis between 1965 and 1983. Complete follow-up through 1984--excluding the first year of follow-up--showed that among 8,517 patients with a diagnosis of alcoholism, 13 cancers occurred, vs. 4.2 expected (standardized incidence ratio (SIR) = 3.1; 95% confidence interval (CI) = 1.6 to 5.3); among 3,589 patients with liver cirrhosis, 59 cancers occurred, vs. 1.7 expected (SIR = 35.1; 95% CI = 26.7 to 45.3), and among 836 patients with both diagnoses, 11 cancers occurred, vs. 0.3 expected (SIR = 34.3; 95% CI = 17.1 to 61.3). Thus, alcoholism alone entailed a moderately increased risk and alcoholism with liver cirrhosis did not increase the high relative risk for liver cancer more than cirrhosis alone. We conclude that alcohol intake may be a liver carcinogen only by being causally involved in the development of cirrhosis; and further, that the risk of developing liver cancer following cirrhosis in this population is similar to or higher than that after chronic hepatitis-B-virus infection in other Western countries.
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.
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.
Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.
Using the Cancer-Environment Registry, which links the incidence of cancer (1961-79) and the 1960 census data on industry and occupation for all employed individuals in Sweden, the occurrence of biliary tract cancer (ICD 7th rev 155.1-.9) was systematically assessed according to occupational and industrial classifications. Data are presented separately for cancer of the gall bladder (ICD 155.1) and other cancers of the biliary tract (ICD 155.2-.9) including cancers of the extrahepatic bile ducts, ampulla of Vater, and unspecified bile passages. Statistically significant increased risks for cancer of the gall bladder were observed for men employed in petroleum refining, papermills, chemical processing, shoemaking, and repairing, and for both men and women employed in textile work. A significant increase in the incidence of other cancers of the biliary tract (mostly cancers of the bile duct) was found for such asbestos related employment as shipbuilding and in the wholesale construction materials industry and among insulation workers. These findings should be considered only as clues to aetiological factors, although several are consistent with earlier observations from other countries.
BACKGROUND: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant condition worldwide, and its incidence has increased markedly in recent decades. Blood transfusions have been implicated as a possible risk factor for non-Hodgkin lymphoma. OBJECTIVE: To determine whether blood transfusions are associated with an elevated risk for non-Hodgkin lymphoma. DESIGN: Population-based, nested case-control study. SETTING: Nationwide cohort in Sweden. PATIENTS: 361 patients with non-Hodgkin lymphoma and 705 matched controls, nested within a population-based cohort of 96795 patients at risk for blood transfusion between 1970 and 1983. Prospectively collected information on exposure was retrieved from computerized transfusion registries. MEASUREMENTS: Odds ratios obtained from conditional logistic regression models were used as measures of relative risks. RESULTS: No association was found between blood transfusions and the risk for non-Hodgkin lymphoma when patients who had received transfusions were compared with patients who had not received transfusions (odds ratio, 0.93 [95% CI, 0.71 to 1.23]). A reduction in risk was seen among persons who received transfusion of blood without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not related to number of transfusions, and no interaction was seen with latency after transfusion. CONCLUSION: The findings in this study do not support previous observations of an association between blood transfusions and the risk for non-Hodgkin lymphoma.
Women undergoing breast reduction surgery have been reported to be at low subsequent risk of breast cancer, especially when the surgery is performed after age 40. To evaluate the age and time-related patterns of cancer risk following surgical removal of breast tissue, we identified 31,910 women who underwent breast reduction surgery from 1965 to 1993 in Sweden using hospital discharge register data. There were 19,975 women (63 percent) under age 40 at surgery. Linkages with Swedish registries for cancer, death, and emigration were based on unique national registration numbers assigned to each Swedish resident. Cancer incidence was contrasted with that expected in the general population based on age- and calendar year-specific data from the nationwide cancer registry. Overall, 161 incident breast cancers were identified during 238,765 person-years of observation (mean, 7.5 years) compared with 223.9 expected (standardized incidence ratio = 0.72; 95 percent confidence interval = 0.61 to 0.84). The reduction in risk of breast cancer was most pronounced for women whose operations were performed after age 50 (SIR = 0.57) and for those followed for more than 5 years (SIR = 0.68). Among women operated on before age 40, risk was nonsignificantly elevated within the first 5 years after surgery (SIR = 1.47; 95 percent CI = 0.89 to 2.30) but tended to be reduced thereafter (SIR = 0.80; 95 percent CI = 0.55 to 1.13). The magnitude of the reduction in risk thus appears directly related to age at surgery. Women followed for an average of 7.5 years after bilateral breast reduction surgery, were at a statistically significant 28 percent decreased risk of breast cancer. The current study is thus consistent with a protective effect following partial removal of breast glandular tissue.