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Biomedical subjects

D G Hoel

Publications and source records attributed to D G Hoel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Early mortality rate of atomic bomb survivors based on House Reconstruction Survey.

This paper studies the mortality rate experienced by over 23,000 A-bomb survivors in Nagasaki between September 1945 and 1950 when the RERF-ABCC initiated the follow-up of the large LSS cohort. The study is based on the data of the 10-year House Reconstruction Survey. As expected, these data show an increasing mortality rate with increasing proximity to the hypocenter of the bomb. What was not anticipated was a higher mortality rate in the 1400-1699 m band than in the closer distance interval of 1200-1399 m. This suggests a possible selective survival among A-bomb survivors. Whether this affects the cancer risk estimates has not as yet been determined.

Dose-Response Relationship, Radiation↗
PubMed1994

Nonlinearity of dose-response functions for carcinogenicity.

Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also obtained for most of these rodent bioassays. It was found that there were no clear relationships between the shape of the carcinogenesis dose-response curve and the result of the short-term test. These observations argue against the concept that carcinogens that are positive in a short-term assay be regulated using a linear dose-response curve and those that are negative be regulated using a sublinear dose-response curve or a safety factor approach.

Animals↗
PubMed1993

Influence of death certificate errors on cancer mortality trends.

BACKGROUND: Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. PURPOSE: Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. METHODS: Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. RESULTS: Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. CONCLUSIONS: The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. IMPLICATIONS: The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning.

Aged↗
PubMed1993

Predictive strategies for selecting 379 NCI/NTP chemicals evaluated for carcinogenic potential: scientific and public health impact.

The a priori criteria used by the National Cancer Institute/National Toxicology Program (NCI/NTP) are described for 379 chemicals selected and evaluated for carcinogenic potential. We classified the chemicals according to exposure and structural categories and evaluated the predictive ability of the scientific selection criteria of chemicals suspected of being carcinogenic in advance of any study. Of the 379 chemicals, 253 (67%) were selected with a suspicion of carcinogenicity; 171 (68%) of these 253 chemicals induced cancer in at least one of the sex-species experiments. The other 126 (33%) chemicals were selected mainly, but not exclusively, on the basis of exposure considerations and production volumes; only 27 (21%) of these were judged to be positive. Overall, 198 (52%) of the 379 chemicals studied induced tumors in at least one organ of one sex of one species, but only 87 (23%) of these 379 chemicals were positive in both species and are considered most likely to present carcinogenic hazards to humans. Importantly, 78 (90%) of these 87 chemicals were selected with a prospective suspicion of carcinogenicity. Although the program has studied only a part of the "Universe of Chemicals" (defined as chemicals to which humans are exposed), the scientific data generated are essential for developing structure activity data bases of potentially hazardous chemical classes and for predicting the carcinogenicity of chemicals not yet studied. Thus, the bioassay program has had beneficial and crucial impacts on public health, as demonstrated by the use of these data by international, Federal, and State regulatory agencies to reduce or eliminate exposures to chemicals shown to be unequivocally carcinogenic in laboratory animals.

Animals↗
PubMed1993

Agricultural exposures and cancer trends in developed countries.

Recent increases have been reported in industrial countries for several sites of cancer. The causes of these increases remain unknown. Efforts should proceed to identify those occupational groups with increases in the same sites, as these may indicate relevant exposures. Two analyses were undertaken: trends in cancer mortality in industrial countries were reviewed to identify recently increasing sites and summaries were compiled of studies on farmers which have shown increased risks for these same sites of cancer. Using data provided by the World Health Organization, age-specific rates were developed for a number of sites of cancer from 1968 to 1986. Trends in the ratio of male to female cancer mortality were also assessed for several of these countries. Based on a literature review by the National Cancer Institute, patterns of cancer in farmers reported in 20 studies from 8 countries are summarized, weighting each study by its size to create combined relative risks. In industrial countries, rates of cancer mortality increased for a number of sites, including melanoma, prostate, non-Hodgkin's lymphoma, multiple myeloma, breast, brain, and kidney cancer. The ratio of male to female cancer mortality (for all sites of cancer excluding lung) has generally increased in several countries during this same time period. Many of the same sites that have increased in the general population have also been found to be increasing in farmers. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain in many surveys.(ABSTRACT TRUNCATED AT 250 WORDS)

Agricultural Workers' Diseases↗
PubMed1993

Medical hypothesis: xenoestrogens as preventable causes of breast cancer.

Changes in documented risk factors for breast cancer and rates of screening cannot completely explain recent increases in incidence or mortality. Established risk factors for breast cancer, including genetics, account for at best 30% of cases. Most of these risk factors can be linked to total lifetime exposure to bioavailable estrogens. Experimental evidence reveals that compounds such as some chlorinated organics, polycyclic aromatic hydrocarbons (PAHs), triazine herbicides, and pharmaceuticals affect estrogen production and metabolism and thus function as xenoestrogens. Many of these xenoestrogenic compounds also experimentally induce mammary carcinogenesis. Recent epidemiologic studies have found that breast fat and serum lipids of women with breast cancer contain significantly elevated levels of some chlorinated organics compared with noncancer controls. As the proportion of inherited breast cancer in the population is small, most breast cancers are due to acquired mutations. Thus, the induction of breast cancer in the majority of cases stems from interactions between host factors, including genetics and environmental carcinogens. We hypothesize that substances such as xenoestrogens increase the risk of breast cancer by mechanisms which include interaction with breast-cancer susceptibility genes. A series of major epidemiologic studies need to be developed to evaluate this hypothesis, including studies of estrogen metabolism, the role of specific xenoestrogenic substances in breast cancer, and relevant genetic-environmental interactions. In addition, experimental studies are needed to evaluate biologic markers of suspect xenoestrogens and biologic markers of host susceptibility and identify pathways of estrogenicity that affect the development of breast cancer. If xenoestrogens do play a role in breast cancer, reductions in exposure will provide an opportunity for primary prevention of this growing disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

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.

Age Factors↗
PubMed1992

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.

Adult↗
PubMed1992

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%.

Animals↗
PubMed1992

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.

Adolescent↗
PubMed1992

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.

Age Factors↗
PubMed1990

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.

Age Factors↗