Risk factors for renal cell carcinoma in Denmark: role of medication and medical history.

BACKGROUND: Several recent studies of risk factors for renal cell carcinoma have indicated that use of diuretics may increase risk of this cancer. It has also been suggested that use of weak analgesics, which are known to increase risk of cancer of the renal pelvis and ureter, may also be associated with an increased risk of renal cell carcinoma--the most frequent type of kidney cancer. METHODS: A population-based case-control study was undertaken to investigate the role of diuretics, other anti-hypertensive drugs, analgesics, and medical history in the aetiology of renal cell carcinoma. The study base was the total Danish population, and 368 histologically verified cases and 396 sex- and age-matched controls who were interviewed from February 1989 to May 1992. RESULTS: Response rates were 76% among cases and 79% among controls. We found no general increase in risk among users of diuretics or analgesics, although women taking loop diuretics and heavy users of acetyl salicylic acid had slightly increased risks. The use of nondiuretic anti-hypertensive medications was associated with decreased risk in women. We found non-significantly increased risks for history of hypertension and other cardiovascular disorders. We also observed elevated risks for urological disorders in both sexes which may be a result of recall bias. CONCLUSION: This study provides only limited support for the suggested association between risk of renal cell carcinoma and use of diuretics and analgesics. The coexistence of renal cell carcinoma and cardiovascular diseases could be caused by risk factors that are common to these conditions.

A case-control and family study of Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a rare disorder of lymphoid and plasma cells characterized by an immunoglobulin M (IgM) monoclonal gammopathy, clinical and immunopathologic similarities with other lymphoproliferative neoplasms, but the etiology of which is unknown. We undertook the first case-control study of this disorder among 65 cases, comprising 87% of all WM patients diagnosed during 1969-1983 in the greater Baltimore, Maryland area. Compared with 213 hospital controls without cancer, cases were slightly better educated, but there were otherwise no differences in sociodemographic factors, history of prior medical conditions, medication use, cigarette smoking, alcohol consumption, specific occupational exposures, employment in any particular industries or occupations, or familial cancer history. Cases were more likely than controls to have first-degree relatives with a history of pneumonia, diphtheria, rheumatic fever, and diabetes mellitus. An exploratory evaluation of immunologic profiles of first-degree relatives of 48% of families of cases revealed that relatives of two cases had asymptomatic IgM (> 750 mg/dl) monoclonal gammopathy and close to 40% of the 109 evaluated had diverse immunologic abnormalities. Larger population-based case-control studies are needed to further evaluate the suggestive evidence of immune dysfunction among families of WM cases.

A comparison of occupational data from death certificates and interviews.

A comparison was made of the occupational data reported on the death certificates of 586 men with their employment history obtained by interviews. Agreement was assessed for 19 occupational and 14 industrial categories of usual employment, with the highest levels of concordance (greater than or equal to 80%) found for agricultural, medical, and public administration activities. Between the two sources of information, there was overall agreement of 56% for usual occupation and 51% for usual industry of employment. Concordance was highest among the 68 self-respondents (usual occupation 66%; usual industry 53%). Among the 518 surrogates, spousal agreement was highest (58% for occupation and 51% for industry). For other surrogate types, agreement was 49% for both industry and occupation. Agreement varied by duration of employment and by level of education, with concordance tending to increase as length of employment and educational attainment rose. These relationships remained when examined by respondent type. Evaluation of agreement levels by age and other study subject characteristics showed little effect on concordance. Review of verbatim data from the interviews and death certificates revealed that most disagreements could be attributed to coding problems caused by vague or misleading information on the death certificates, although some disconcordance was due to uncodable and missing information in the interview history. Based on results from this and prior studies, the value of occupational data derived from death certificates in epidemiologic studies may be limited, although the addition of explicit instructions on the death certificate itself may aid in providing more useful and complete information for usual employment.

Comparison of next-of-kin with self-respondents regarding questions on cigarette, coffee, and alcohol consumption.

Using the same questionnaire, personnel, and field procedures, we conducted interviews in 1985 with the next-of-kin of 108 deceased study subjects, and with 197 surviving subjects who had been interviewed earlier in a 1980 case-control study. Concordance in response between the two interviews for cigarette smoking, coffee drinking, and alcoholic beverage intake was high, generally 90% or above. Next-of-kin, particularly spouses, provided information as reliable as the self-informants for cigarette smoking and coffee consumption, but showed a somewhat higher discrepancy rate for alcohol drinking. Thus, surrogates, especially spouses, appear to be an accurate source of information in epidemiologic investigations.

Relation of analgesic use to renal cancer: population-based findings.

A population-based case-control study of renal cancer (495 cases of renal cell cancer, 74 cases of renal pelvis cancer, and 697 controls) was conducted in the Minneapolis-St. Paul 7-county metropolitan area. Information was obtained on a large number of variables, including the use of analgesic drugs. Long-term use (greater than 36 mo) of phenacetin-containing products was associated in both sexes with a twofold increased risk for renal cell cancer. Long-term use of phenacetin- and acetaminophen-containing products was associated with elevated risks of nearly threefold to eightfold for cancer of the renal pelvis. The separate effects of these analgesics could not be adequately assessed because most long-term users took both products.

Problems in the use of dead controls in case-control studies. II. Effect of excluding certain causes of death.

A recent comparison of 493 dead and 697 living controls from a case-control study of cancer in the Minneapolis-St. Paul area showed that the dead controls of both sexes were reported to have been significantly heavier consumers of cigarettes, hard liquor, beer, and certain drugs, and to have had more adulthood diseases than living controls. The present analysis examines the effect of excluding causes of death associated with those exposures found in excess in the dead controls. Exclusion of individuals with smoking-related causes of death reduced but did not eliminate the excess of cigarette smokers among the dead controls. Deletion of individuals with alcohol-related causes of death only slightly reduced the excess among dead controls. Adjustment for cigarette smoking, however, nearly eliminated the association with alcohol consumption, particularly among males. For certain adulthood diseases and medications, the exclusion of individuals with exposure-associated causes of death also virtually eliminated the excesses found in the dead controls when compared with the living controls. Thus, it appears that even after extensive exclusion of smoking-related causes of death, the association between dead controls and cigarette smoking still remains, and the use of dead controls in case-control studies where cigarette smoking is the risk factor being evaluated may lead to a biased underestimated of risk. For the other exposures found in significant excess among the dead controls, the exclusion of exposure-related causes of death and proper adjustment for confounders may eliminate much or all of the excess.

Petroleum-related employment and renal cell cancer.

The risk of renal cell cancer among those in occupations with potential for petroleum exposure was evaluated in a large population-based case-control study. Overall there was little difference between the cases and control groups in the proportion of persons with petroleum-related employment (odds ratio = 1.0). Among gasoline station attendants, a slight upward trend in risk was observed with increasing duration of employment. The significance of this association is not clear, but further research is needed in light of recent animal findings linking gasoline exposure to renal cancer.

Problems in the use of dead controls in case-control studies. I. General results.

A recently completed case-control study in the Minneapolis-St. Paul area using population-based living controls and dead controls afforded the opportunity to compare these two control groups on their exposure histories. Detailed information was obtained by interview from 697 living controls and the next of kin of 493 dead controls. The dead controls of both sexes were reported to have been significantly heavier cigarette smokers compared with living controls, as well as heavier consumers of hard liquor, beer, and drugs, and to have had more adulthood diseases. There were no consistent differences between the control groups for consumption of nonalcoholic beverages, some aspects of diet, ethnic and religious background, usual occupation, and residential history. It appears that exposures associated with premature death are overrepresented in dead controls compared with living controls, while those variables not associated with premature mortality are distributed more or less similarly between the two groups.

A population--based case--control study of renal cell carcinoma.

A population-based case-control study of renal cell carcinoma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.1-2.4) and among women of 1.9 (1.3-3.0). A statistically significant dose response was observed in both sexes for pack-years of cigarette use. On the basis of calculations of attributable risk, it was estimated that 30% of renal cell cancers among men and 24% among women were due to smoking. High relative adult weight as measured by the body mass index (BMI) was found to be a major risk factor among women but not among men, with those in the highest 5% of the BMI having an OR of 5.9 (1.8-20.4) in comparison to the lowest quartile. This association with excess weight was not seen at age 20, but it became more pronounced with increasing age, suggesting that the primary influence of weight gain is during the late stages of renal carcinogenesis. Excess risks were also related to ethnic background (particularly, German), which may account in part for the elevated incidence of renal cancer in the North Central area of the United States. In addition, positive associations were observed for long-term use of phenacetin-containing analgesics, heavy meat consumption, and heavy tea drinking (females only). An occupational clue was provided by an increased risk for exposure to petroleum, tar, and pitch products. Excesses of certain urologic and cardiovascular diseases were also observed among the cases compared to controls.

Etiology of cancer of the renal pelvis.

A population-based case--control interview study of cancer of the renal pelvis (74 cases and 697 controls) conducted in the Minneapolis--St. Paul metropolitan area showed cigarette smoking to be the major cause of this cancer. The odds ratio (OR) for cigarette smoking was 7.6 among males [95% confidence interval (CI): 2.2-31.5] and 5.8 among females (95% CI: 2.0-17.3), with the OR exceeding 10 for heavy smokers of both sexes. Long-term use of analgesics and several occupational exposures were also found to be risk factors. In addition, there were unexpected positive associations among females for heavy tea consumption and for use of estrogen medications, although the significance of these relationships remains to be clarified.