The one-step (Peto) method for obtaining pooled effect estimates can yield extremely biased results when applied to unbalanced data. Even for balanced studies, the one-step estimate may incorporate an unacceptable degree of bias. In place of the one-step estimate, we recommend use of ordinary Mantel-Haenszel, weighted least squares, or maximum likelihood estimates whenever the total number of events is adequate for such methods. If the total number of events is small, we recommend exact methods.

AimIn the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. Methods All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. Results 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified.

OBJECTIVES. To update mortality risks for Navajo uranium miners, a retrospective cohort mortality study was conducted of 757 Navajos from the cohort of Colorado Plateau uranium miners. METHODS. Vital status was followed from 1960 to 1990. Standardized mortality ratios were estimated, with combined New Mexico and Arizona non-White mortality rates used for comparison. Cox regression models were used to evaluate exposure-response relationships. RESULTS. Elevated standardized mortality ratios were found for lung cancer (3.3), tuberculosis (2.6), and pneumoconioses and other respiratory diseases (2.6). Lowered ratios were found for heart disease (0.6), circulatory disease (0.4), and liver cirrhosis (0.5). The estimated relative risk for a 5-year duration of exposure vs none was 3.7 for lung cancer, 2.1 for pneumoconioses and other respiratory diseases, and 2.0 for tuberculosis. The relative risk for lung cancer was 6.9 for the midrange of cumulative exposure to radon progeny compared with the least exposed. CONCLUSIONS. Findings were consistent with those from previous studies. Twenty-three years after their last exposure to radon progeny, these light-smoking Navajo miners continue to face excess mortality risks from lung cancer and pneumoconioses and other respiratory diseases.

Many occupational studies analyze trends between cumulative exposure and mortality. The authors show that such trends are, in general, negatively confounded by employment status. Mortality rates for workers who leave work ("inactive" workers) are higher than for active workers because some workers leave because they are ill. The percentage of inactive relative to active person-time is higher in low categories of cumulative exposure, causing employment status to act as a negative confounder of exposure-response trends (the opposite occurs for time-since-hire). We illustrate these phenomena using 10 "negative" mortality studies, in which adjustment for employment status removes false trends. However, adjustment for employment status will lead to biased estimates when it acts as an intermediate variable between cumulative exposure and death, as occurs directly when exposure causes a disabling disease that, in turn, causes death or indirectly when exposure causes workers to leave work. The authors illustrate this problem using simulated follow-up data for leaving, disease incidence, and mortality. In the null case in which cumulative exposure affects neither disease incidence (or mortality) nor leaving rates, employment status indeed acts as a negative confounder of exposure-response trends, and traditional adjustment eliminates this confounding. However, when cumulative exposure affects disease incidence or rates of leaving, adjustment for employment status will not be adequate. Employment status falls under the general rubric of variables that are simultaneously confounders and intermediate variables.

To address earlier reports of excess cancer mortality associated with employment at a large transformer manufacturing plant, each plant operation was rated for seven exposures: Pyranol (a mixture of polychlorinated biphenyls and trichlorobenzene), trichloroethylene, benzene, mixed solvents, asbestos, synthetic resins, and machining fluids. Site-specific cancer deaths among active or retired employees were cases; controls were selected from deaths (primarily cardiovascular deaths) presumed to be unassociated with any of the study exposures. Using job records, we then computed person-years of exposure for each subject. All subjects were white males. The only unequivocal association was that of resin systems with lung cancer (odds ratio = 2.2 at 16.6 years of exposure, P = 0.001, in a multiple logistic regression including asbestos, age, year of death, and year of hire). Certain other odds ratios appeared larger, but no other association was so robust and remained as distinct after considering the multiplicity of comparisons. Study power was very limited for most associations, and several biases may have affected our results. Nevertheless, further investigation of synthetic resin systems of the type used in the study plant appears warranted.