Biomedical subjects
D G Hoel
Publications and source records attributed to D G Hoel.
Trends in cancer mortality in 15 industrialized countries, 1969-1986.
BACKGROUND: Assessing trends in cancer provides a means for gauging progress against the disease, estimating future demands for care and treatment, and suggesting clues about shifting causal factors that may account for the more recent changes. PURPOSE: This study was designed to evaluate trends in the major sites of cancer associated with high mortality rates in 15 industrialized countries. To highlight differences among regions, we grouped these countries into six geographic areas: United States, Eastern Europe, Western Europe, East Asia, Oceania, and Nordic countries. In addition, cancer mortality trends in these regions were compared with incidence patterns in the United States. METHODS: Data provided by the World Health Organization were used to evaluate age-specific mortality trends from 1969 through 1986 for lung, breast, prostate, stomach, and colorectal cancers and for all other sites considered as a group. We also assembled and analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the same sites and age groups from 1973 through 1986. RESULTS: Over the period 1969 through 1986, recorded cancer mortality in persons aged 45 years and older in the six regions studied has increased for lung, breast, and prostate cancers in most age groups, while the decline in stomach cancer mortality is substantial. The increase in lung cancer deaths in men aged 45-54 years has slowed greatly or reversed in all areas except Eastern Europe and East Asia. Trends for intestinal cancer vary by age and region. For all other sites considered as a group, increases have occurred for persons older than 64 years in most regions. In Eastern Europe, there are disturbingly high rates and rapid increases for several of the major forms of cancer in persons aged 45-54 years. In general, trends for cancer incidence in the United States parallel those for mortality. For intestinal cancer, however, incidence has increased while mortality has declined. CONCLUSIONS: The trends we report cannot be explained solely by changes in cigarette smoking or aging. Other causes of changes in cancer incidence and mortality need to be determined. IMPLICATIONS: The increasing and decreasing trends in mortality from and incidence of cancer that we found are important for health care planning and may also suggest opportunities for research in cancer prevention.
Exploring time trends in cancer incidence.
We examined incidence time-trends for lung, stomach, intestinal, prostate, and breast cancer among Whites diagnosed in the United States between 1973 and 1987. For each sex and five-year age group, we modeled cancer incidence as a log-linear function of diagnosis-year to permit extrapolation over time and simple summarization of trends. Comparisons with nonparametric estimates show that, except for breast cancer, the model performs well. Plots of the annual percent change in incidence cf age illustrate the way in which time trends depend on age. Between 1973 and 1987, stomach cancer incidence decreased by about two percent per year. The annual change in lung cancer incidence progressed from a two to three percent decrease in persons under age 40 to an increase of two percent in men and eight percent in women by age 80. Intestinal cancer incidence decreased annually by as much as three percent in persons under age 50, remained constant in women aged 50 to 74, and otherwise increased about one percent per year. The annual increase in prostate cancer incidence declined from about six percent in men under age 40 to about two percent in men over age 80. After a surge in female breast-cancer diagnoses in 1974, the annual increase in incidence between 1980 and 1987 stabilized at four to six percent.
Omeprazole, cytochrome P450, and chemical carcinogenesis.
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Concordance of carcinogenic response between rodent species: potency dependence and potential underestimation.
The use of average qualitative concordance between two bioassay endpoints is considered, with emphasis directed at agreement between rats and mice from results of long-term carcinogenicity studies. It is noted that concordance varies as a function of the underlying potency or toxicity of the chemicals over which the averaging is performed. Thus, the averaging process dilutes large observed concordances from potent chemicals, and possibly inflates lower observed concordances from weakly active chemicals. Stratification over some measure of potency is suggested as a method for taking these effects into account. Statistical simulations of concordance analyses limited to low-potency ranges are employed to examine the concordance measure in greater detail. It is seen that at low potencies, observed concordance is consistently underestimated, reaching maximum levels of only about 80%.
Figuring out cancer.
Cancer continues to increase throughout the industrial world. Aging of the population, smoking habits, and improvements in diagnosis do not account completely for these patterns. About 5 percent of cancers occur in persons under age 45, while 65 percent of all cancers occur in persons over age 65. For this older age group, many of their most common tumors, in addition to those linked with smoking, are not curable and appear to be increasing in incidence as well as mortality in a number of industrial countries. Evaluating cancer causes by looking at an age-adjusted rate obscures important differences that are occurring at different age groups. In order to reduce the cancer burden further, it is important to look for bona fide explanations of recent shifts in cancer patterns, especially those not related to cigarette smoking or other habits.
Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 3. Noncancer mortality based on the revised doses (DS86).
Deaths in the RERF Life Span Study (LSS) sample have been determined for the years 1950-1985 and an analysis of cancer mortality with the revised DS86 doses has been described separately. In this report, we examine the relationship to dose of deaths from all diseases other than cancer. Although the evidence is still limited, there seems to be an excess risk from noncancer death at high doses (2 or 3 Gy and over). Statistically, a pure quadratic or a linear-threshold model [the estimated threshold dose is 1.4 Gy (0.6-2.8 Gy)] is found to fit better than a simple linear or linear-quadratic model. This increase in noncancer mortality is statistically demonstrable, generally, after 1965 and among the younger survivors (less than 40 at the time of the bombing), suggesting a sensitivity for this age group. For specific causes of death, an excess in relative risk at the high dose level, that is, 2 Gy or more, is seen in circulatory and digestive diseases. The relative risk is, however, much smaller than that for cancer. These findings, based as they are on death certificates, have their limitations. Most significant, perhaps, is the possible erroneous attribution of radiation-related cancer deaths to other causes. At present, the contribution such errors may make to the apparent increase in non-cancer deaths at the higher doses cannot be estimated as rigorously as is obviously desirable. However, even now, this increase does not appear to be fully explicable in terms of errors in classification. Further follow-up of mortality in this LSS cohort as well as disease revealed by the biennial physical examinations of the morbidity subsample (Adult Health Study) of the LSS cohort will be needed to confirm this suggestion of a radiation-related increase in mortality from causes other than cancer, and to determine whether it results in a demonstrable life shortening among the heavily exposed A-bomb survivors.
Mechanistic and statistical insight into the large carcinogenesis bioassays on N-nitrosodiethylamine and N-nitrosodimethylamine.
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Objectives of the collaborative study on the genetic toxicology of 2-amino-N6-hydroxyadenine: an exercise in genetic risk assessment.
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Assumptions of the HERP Index.
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Using mortality data to estimate radiation effects on breast cancer incidence.
In this paper we combine Japanese data on radiation exposure and cancer mortality with U.S. data on cancer incidence and lethality to estimate the effects of ionizing radiation on cancer incidence. The analysis is based on the mathematical relationship between the mortality rate and the incidence and lethality rates, as well as on statistical models that relate Japanese incidence rates to U.S. incidence rates and radiation risk factors. Our approach assumes that the risk of death from causes other than the cancer does not depend on whether or not the cancer is present, and among individuals with the cancer, the risk of death attributable to the cancer is the same in Japan and the U.S. and is not affected by radiation exposure. In particular, we focus on the incidence of breast cancer in Japanese women and how this incidence is affected by radiation risk factors. The analysis uses Japanese exposure and mortality data from the Radiation Effects Research Foundation study of atomic bomb survivors and U.S. incidence and lethality data from the Surveillance, Epidemiology, and End Results Registry. Even without Japanese incidence data, we obtain reasonable estimates of the incidence of breast cancer in unexposed Japanese women and identify the radiation risk factors that affect this incidence. Our analysis demonstrates that the age at exposure is an important risk factor, but that the incidence of breast cancer is not affected by the city of residence (Nagasaki versus Hiroshima) or the time since exposure.
Biologically based models for risk assessment.
The modelling problems associated with the estimation of risks from long-term chemical exposures at low dose levels represent a statistical and mathematical challenge with special relevance to environmental research. Determining an adequate model for estimating the relationship between dose and response is critical to reducing potential bias in the risk estimation process. This paper discusses the various assumptions and models used in carcinogenic risk assessment. The emphasis is on our ability to accurately determine the magnitude of the carcinogenic risk, the shape of the dose-response relationship and the overall variability of the risk estimates.
Benzene risk assessments: review and update.
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Statistical design of toxicity assays: role of genetic structure of test animal population.
This paper concerns certain statistical aspects of the problem of among-strain differences in cancer susceptibility and how these differences may affect the design of toxicity assays. First, the data of Innes et al. (1969) were examined to investigate the magnitude of within-study, between-strain differences in tumor induction. Although there was a very high overall association between mouse strains with respect to the induction of hepatomas, evidence of strain-to-strain variability was found for several compounds. Next, a number of long-term carcinogenicity studies with DDT were considered, and among-strain differences in cancer susceptibility for this compound were noted. Finally, it was shown that if susceptible subgroups do exist, and certain simplifying assumptions are made, then in many cases tumor increases can be detected more readily by studying several inbred mouse strains rather than a single outbred stock.
Animal experimentation and its relevance to man.
The problem of quantitatively estimating human cancer risk based upon animal carcinogenesis studies is reviewed. Mathematical functions for dose-response relationships are discussed with particular emphasis on multistage models. These models are based upon a single cell somatic mutation theory for the carcinogenesis process. It is shown that the multistage model and others which incorporate background additively are well approximated in low dose region by a linear function. The relationship between time-to-tumor and the multistage model is indicated. This relationship is important when dealing with less than life time exposure such as with data from many occupational studies. Design of bioassay experiments and its impact on risk estimation is noted. Finally, the problem of species-to-species extrapolation is considered.
Statistical approaches to toxicological data.
Statistical techniques as applied to toxicological data are discussed. Issues concerning statistical hypothesis testing and combining studies are considered as well as design of experiments. The problems surrounding risk assessment are also mentioned.
Sequential methods in genetic risk assessment.
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Occupational carcinogenesis. Statistical extrapolation methods for estimating risks from animal data.
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